Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: Implications for pathogenesis

Endocrine Reviews

Volumn 34, Issue 3, 2013, Pages 339-376

  Kraggerud, Sigrid Marie ^a,d   Hoei Hansen, Christina E ^e   Alagaratnam, Sharmini ^a,c,d   Skotheim, Rolf I ^a,c,d   Abeler, Vera M ^b   Meyts, Ewa Rajpert De ^e   Lothe, Ragnhild A ^a,c,d  

^a Center of Clinical Epidemiology   (Norway)

^b OSLO UNIVERSITY HOSPITAL   (Norway)

^c OSLO UNIVERSITY HOSPITAL   (Norway)

^d UNIVERSITY OF OSLO   (Norway)

^e Rigshospitalet   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALINE PHOSPHATASE; BETA CATENIN; BLEOMYCIN; BONE MORPHOGENETIC PROTEIN; CASPASE 8; CHORIONIC GONADOTROPIN; CISPLATIN; CONNEXIN 43; DNA METHYLTRANSFERASE 3B; ETOPOSIDE; FORKHEAD TRANSCRIPTION FACTOR; GAP JUNCTION PROTEIN; GONADOTROPIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 6; LACTATE DEHYDROGENASE; LYMPHOID ENHANCER FACTOR 1; MICRORNA 375; P CADHERIN; TRANSCRIPTION FACTOR 7 LIKE 2; TRANSCRIPTION FACTOR AP 2; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR GATA 6; TRANSFORMING GROWTH FACTOR BETA; VASCULOTROPIN; WNT4 PROTEIN; ZINC FINGER PROTEIN;

ANDROGEN INSENSITIVITY SYNDROME; CANCER COMBINATION CHEMOTHERAPY; CANCER EPIDEMIOLOGY; CANCER INCIDENCE; CANCER PROGNOSIS; CANCER SURVIVAL; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CHROMATIN CONDENSATION; CHROMOSOME 12; CHROMOSOME ARM; COMPARATIVE GENOMIC HYBRIDIZATION; DELAYED PUBERTY; DIFFERENTIAL DIAGNOSIS; DNA METHYLATION; DOWN REGULATION; DYSGERMINOMA; ECTOPIC PREGNANCY; EMBRYO DEVELOPMENT; EMBRYONAL CARCINOMA; GENE DOSAGE; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE MUTATION; GENITAL MALFORMATION; GERM CELL TUMOR; GONAD DEVELOPMENT; GONADAL DYSGENESIS; HETEROZYGOSITY LOSS; HUMAN; HYPERANDROGENISM; IN SITU HYBRIDIZATION; IN VITRO STUDY; IN VIVO STUDY; ISOCHROMOSOME; KARYOTYPE; LYMPHOCYTIC INFILTRATION; MALE INFERTILITY; MALIGNANT TRANSFORMATION; MEIOTIC PROPHASE I; META ANALYSIS (TOPIC); MICROSATELLITE INSTABILITY; MISMATCH REPAIR; OVARY CANCER; OVARY CARCINOMA; OVARY DEVELOPMENT; OVARY TERATOMA; OVARY TUMOR; OVERALL SURVIVAL; PATHOGENESIS; PLOIDY; PLURIPOTENT STEM CELL; PRIMARY AMENORRHEA; PRIMORDIAL GERM CELL; PRINCIPAL COMPONENT ANALYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; SEMINOMA; SEX DIFFERENTIATION; SEX DIFFERENTIATION DISORDER; SHORT STATURE; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SURVIVAL RATE; TESTIS CANCER; UPREGULATION; VAGINA BLEEDING; WNT SIGNALING PATHWAY; Y CHROMOSOME; YOLK SAC TUMOR;

ANIMALS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MALE; NEOPLASM PROTEINS; NEOPLASMS, GERM CELL AND EMBRYONAL; OVARIAN NEOPLASMS; TESTICULAR NEOPLASMS;

EID: 84878666299     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2012-1045     Document Type: Review

References (344)

1. Clement PB, Young RH. Ovarian surface epithelial-stromal tumors. In: Mills SE, ed. Sternberg's Diagnostic Surgical Pathology. 5th ed. Philadelphia, PA: Lippincott Williams, Wilkins; 2009;2278-2308.
2. Young RH, Clement PB. Sex cord-stromal, steroid cell, and germ cell tumors of the ovary. In: Mills SE, ed. Sternberg's Diagnostic Surgical Pathology. 5th ed. Philadelphia, PA: Lippincott Williams, Wilkins; 2009;2309-2341.
3. Palmer RD, Nicholson JC, Hale JP. Management of germ cell tumours in childhood. Curr Paediatr. 2003;13:213-220.
4. Pleskacova J, Hersmus R, Oosterhuis JW, et al. Tumor risk in disorders of sex development. Sex Dev. 2010;4:259-269.
5. Nogales F, Talerman A, Kubik-Huch RA, Tavassoli FA, Devouassoux-Shisheboran M. Germ cell tumours. In: Tavassoli FA, Deville P, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: IARC Press; 2003:163-175.
6. Roth LM, Talerman A. Recent advances in the pathology and classification of ovarian germ cell tumors. Int J Gynecol Pathol. 2006;25:305-320.
7. Hu L, McArthur C, Jaffe RB. Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant. Br J Cancer. 2010;102:1276-1283.
8. Peng S, Maihle NJ, Huang Y. Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene. 2010;29:2153-2159.
9. Scully RE. Ovarian tumors. A review. Am J Pathol. 1977; 87:686-720.
10. Oosterhuis JW, Looijenga LH. Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer. 2005;5: 210-222.
11. Quirk JT, Natarajan N. Ovarian cancer incidence in the United States, 1992-1999. Gynecol Oncol. 2005;97:519-523.
12. Quirk JT, Natarajan N, Mettlin CJ. Age-specific ovarian cancer incidence rate patterns in the United States. Gynecol Oncol. 2005;99:248-250.
13. dos Santos Silva I, Swerdlow AJ. Ovarian germ cell malignancies in England: epidemiological parallels with testicular cancer. Br J Cancer. 1991;63:814-818.
14. Møller H, Evans H. Epidemiology of gonadal germ cell cancer in males and females. APMIS. 2003;111:43-48.
15. Brookfield KF, Cheung MC, Koniaris LG, Sola JE, Fischer AC. A population-based analysis of 1037 malignant ovarian tumors in the pediatric population. J Surg Res. 2009; 156:45-49.
16. Guillem V, Poveda A. Germ cell tumours of the ovary. Clin Transl Oncol. 2007;9:237-243.
17. Walker AH, Ross RK, Pike MC, Henderson BE.Apossible rising incidence of malignant germ cell tumours in young women. Br J Cancer. 1984;49:669-672.
18. Smith HO, Berwick M, Verschraegen CF, et al. Incidence and survival rates for female malignant germ cell tumors. Obstet Gynecol. 2006;107:1075-1085.
19. Pectasides D, Pectasides E, Kassanos D. Germ cell tumors of the ovary. Cancer Treat Rev. 2008;34:427-441.
20. Parkinson CA, Hatcher HM, Ajithkumar TV. Management of malignant ovarian germ cell tumors. Obstet Gynecol Surv. 2011;66:507-514.
21. Gershenson DM. Management of ovarian germ cell tumors. J Clin Oncol. 2007;25:2938-2943.
22. Murugaesu N, Schmid P, Dancey G, et al. Malignant ovarian germ cell tumors: Identification of novel prognostic markers and long-term outcome after multimodality treatment. J Clin Oncol. 2006;24:4862-4866.
23. Weinberg LE, Lurain JR, Singh DK, Schink JC. Survival and reproductive outcomes in women treated for malignant ovarian germ cell tumors. Gynecol Oncol. 2011;121: 285-289.
24. Luis IV, Coleman R. Ovarian germ cell malignancy: a heterogeneous tumour requiring supra-regional management. Eur J Gynaecol Oncol. 2011;32:387-392.
25. Low JJ, Perrin LC, Crandon AJ, Hacker NF. Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases. Cancer. 2000;89:391-398.
26. Low JJ, Ilancheran A, Ng JS. Malignant ovarian germ-cell tumours. Best Pract Res Clin Obstet Gynaecol. 2012;26: 347-355.
27. Zanetta G, Bonazzi C, Cantu MG, Locatelli A, Bratina G, Mangioni C. Survival and reproductive function after treatment of malignant germ cell ovarian tumors. J Clin Oncol. 2001;19:1015-1020.
28. Rozenholc A, Abdulcadir J, Pelte MF, Petignat P. A pelvic mass on ultrasonography and high human chorionic gonadotropin level: not always an ectopic pregnancy. BMJ Case Rep. 2012; doi: 10.1136/bcr.01.2012.5577.
29. McKnight KK, Bates J. Atypical presentation and management dilemma of mixed gonadal dysgenesis. Fertil Steril. 2011;95:291.e7-291.e9.
30. Dennedy MC, Smith D, O'Shea D, McKenna TJ. Investigation of patients with atypical or severe hyperandrogenaemia including androgen-secreting ovarian teratoma. Eur J Endocrinol. 2010;162:213-220.
31. Gershenson DM. Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors. J Clin Oncol. 1988;6:270-275.
32. Hale GA, Marina NM, Jones-Wallace D, Greenwald CA, Jenkins JJ, Rao BN, Luo X, Hudson MM. Late effects of treatment for germ cell tumors during childhood and adolescence. J Pediatr Hematol Oncol. 1999;21:115-122.
33. Brewer M, Gershenson DM, Herzog CE, Mitchell MF, Silva EG, Wharton JT. Outcome and reproductive function after chemotherapy for ovarian dysgerminoma. J Clin Oncol. 1999;17:2670-2675.
34. Swenson MM, MacLeod JS, Williams SD, Miller AM, Champion VL. Quality of life after among ovarian germ cell cancer survivors: a narrative analysis. Oncol Nurs Forum. 2003;30:E48-E54.
35. de Vos FY, Nuver J, Willemse PH, et al. Long-term survivors of ovarian malignancies after cisplatin-based chemotherapy: cardiovascular risk factors and signs of vascular damage. Eur J Cancer. 2004;40:696-700.
36. Champion V, Williams SD, Miller A, et al. Quality of life in long-term survivors of ovarian germ cell tumors: a gynecologic oncology group study. Gynecol Oncol. 2007; 105:687-694.
37. Monahan PO, Champion VL, Zhao Q, et al. Case-control comparison of quality of life in long-term ovarian germ cell tumor survivors: a gynecologic oncology group study. J Psychosoc Oncol. 2008;26:19-42.
38. Matei D, Miller AM, Monahan P, et al. Chronic physical effects and health care utilization in long-term ovarian germ cell tumor survivors: a gynecologic oncology group study. J Clin Oncol. 2009;27:4142-4149.
39. Gershenson DM, Miller AM, Champion VL, et al. Reproductive and sexual function after platinum-based chemotherapy in long-term ovarian germ cell tumor survivors: a gynecologic oncology group study. J Clin Oncol. 2007;25: 2792-2797.
40. Fung C, Vaughn DJ. Complications associated with chemotherapy in testicular cancer management. Nat Rev Urol. 2011;8:213-222.
41. Winter C, Albers P. Testicular germ cell tumors: pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2011;7:43-53.
42. Fosså SD, Oldenburg J, Dahl AA. Short-and long-term morbidity after treatment for testicular cancer. BJU Int. 2009;104:1418-1422.
43. Oldenburg J, Kraggerud SM, Brydoy M, Cvancarova M, Lothe RA, Fosså SD. Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-s-transferase-P1 and-M1, a retrospective cross sectional study. J Transl Med. 2007;5:70.
44. Oldenburg J, Kraggerud SM, Cvancarova M, Lothe RA, Fossa SD. Cisplatin-induced long-term hearing impairment is associated with specific glutathione S-transferase genotypes in testicular cancer survivors. J Clin Oncol. 2007;25:708-714.
45. Jiménez R. Ovarian organogenesis in mammals: mice cannot tell us everything. Sex Dev. 2009;3:291-301.
46. Oktem O, Oktay K. The ovary. Ann N Y Acad Sci. 2008; 1127:1-9.
47. Cools M, Looijenga LHJ, Wolffenbuttel K, Drop S. Disorders of sex development: update on the genetic background, terminology and risk for the development of germ cell tumors. World J Pediatr. 2009;5:93-102.
48. SaitouM.Germcell specification in mice. Curr Opin Genet Dev. 2009;19:386-395.
49. Oktem O, Oktay K. Stem cells. Ann N Y Acad Sci. 2008; 1127:20-26.
50. Saitou M, Yamaji M. Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences. Reproduction. 2010;139:931-942.
51. Tres LL, Rosselot C, Kierszenbaum AL. Primordial germ cells: what does it take to be alive? Mol Reprod Dev. 2004; 68:1-4.
52. Schäfer S, Anschlag J, Nettersheim D, Haas N, Pawig L,Schorle H. The role of BLIMP1 and its putative downstream target TFAP2C in germ cell development and germ cell tumours. Int J Androl. 2011;34:e152-e159.
53. Kurimoto K, Yamaji M, Seki Y, Saitou M. Specification of the germ cell lineage in mice: a process orchestrated by the PR-domain proteins, Blimp1 and Prdm14. Cell Cycle. 2008;7:3514-3518.
54. Hart AH, Hartley L, Parker K, et al. The pluripotency homeobox gene NANOG is expressed in human germ cell tumors. Cancer. 2005;104:2092-2098.
55. Hoei-Hansen CE, Kraggerud SM, Abeler VM, Kaern J, Rajpert-De Meyts E, Lothe RA. Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers. Mol Cancer. 2007;6:12.
56. Hoei-Hansen CE, Nielsen JE, Almstrup K, et al. Transcription factor AP-2g is a developmentally regulated marker of testicular carcinoma in situ and germ cell tumors. Clin Cancer Res. 2004;10:8521-8530.
57. Hoei-Hansen CE, Almstrup K, Nielsen JE, et al. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology. 2005;47:48-56.
58. Hersmus R, de Leeuw BH, Wolffenbuttel KP, et al. New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD). Mol Cell Endocrinol. 2008; 291:1-10.
59. Looijenga LH, Hersmus R, de Leeuw BH, et al. Gonadal tumours and DSD. Best Pract Res Clin Endocrinol. 2010; 24:291-310.
60. Cheng L, SungMT,Cossu-Rocca P, et al.OCT4:biological functions and clinical applications as a marker of germ cell neoplasia. J Pathol. 2007;211:1-9.
61. Molyneaux K, Wylie C. Primordial germ cell migration. Int J Dev Biol. 2004;48:537-544.
62. Møllgård K, Jespersen A, Lutterodt MC, Yding Andersen C, Høyer PE, Byskov AG. Human primordial germ cells migrate along nerve fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge. Mol Hum Reprod. 2010;16:621-631.
63. Wilhelm D, Palmer S, Koopman P. Sex determination and gonadal development in mammals. Physiol Rev. 2007;87: 1-28.
64. Bowles J, Knight D, Smith C, et al. Retinoid signaling determines germ cell fate in mice. Science. 2006;312:596-600.
65. Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, PageDC.Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A. 2006; 103:2474-2479.
66. Souquet B, Tourpin S, Messiaen S, Moison D, Habert R, Livera G. Nodal signaling regulates the entry into meiosis in fetal germ cells. Endocrinology. 2012;153:2466-2473.
67. Jørgensen A, Nielsen JE, Blomberg Jensen M, Graem N, Rajpert-De Meyts E. Analysis of meiosis regulators in human gonads: a sexually dimorphic spatio-temporal expression pattern suggests involvement of DMRT1 in meiotic entry. Mol Hum Reprod. 2012;18:523-534.
68. Honecker F, Stoop H, de Krijger RR, Lau YF, Bokemeyer C, Looijenga LH. Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells. J Pathol. 2004;203:849-857.
69. Pauls K, Schorle H, Jeske W, et al. Spatial expression of germ cell markers during maturation of human fetal male gonads: an immunohistochemical study. Hum Reprod. 2006;21:397-404.
70. Rajpert-De Meyts E, Hanstein R, Jørgensen N, Græm N, Vogt PH, Skakkebæk NE. Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Hum Reprod. 2004;19:1338-1344.
71. Stoop H, Honecker F, Cools M, de Krijger R, Bokemeyer C, Looijenga LH. Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study. Hum Reprod. 2005;20: 1466-1476.
72. Brennan J, Capel B. One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 2004;5:509-521.
73. Parma P, Radi O, Vidal V, et al. R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet. 2006;38:1304-1309.
74. Mandel H, Shemer R, Borochowitz ZU, et al. SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet. 2008;82:39-47.
75. Uhlenhaut NH, Jakob S, Anlag K, et al. Somatic sex reprogramming of adult ovaries to testes byFOXL2ablation. Cell. 2009;139:1130-1142.
76. Tomaselli S, Megiorni F, Lin L, et al. Human RSPO1/R-spondin1 is expressed during early ovary development and augments β-catenin signaling. PLoS One. 2011;6: e16366.
77. Tevosian SG, Manuylov NL. To β or not to β: canonical β-catenin signaling pathway and ovarian development. Dev Dynam. 2008;237:3672-3680.
78. Hersmus R, Kalfa N, de Leeuw B, et al. FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD). J Pathol. 2008;215:31-38.
79. Pannetier M, Pailhoux E. FOXL2, le gardien de l'identité ovarienne. Med Sci (Paris). 2010;26:470-473.
80. Jamieson S, Fuller PJ. Molecular pathogenesis of granulosa cell tumors of the ovary. Endocr Rev. 2012;33:109-144.
81. Hes O, Vanecek T, Petersson F, et al. Mutational analysis (c. 402C>G) of the FOXL2 gene and immunohistochemical expression of the FOXL2 protein in testicular adult type granulosa cell tumors and incompletely differentiated sex cord stromal tumors. Appl Immunohistochem Mol Morphol. 2011;19:347-351.
82. Matson CK, Murphy MW, Sarver AL, Griswold MD, Bardwell VJ, Zarkower D. DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature. 2011;476:101-104.
83. Gill ME, Hu YC, Lin Y, Page DC. Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells. Proc Natl Acad Sci U S A. 2011;108:7443-7448.
84. Houmard B, Small C, Yang L, et al. Global gene expression in the human fetal testis and ovary. Biol Reprod. 2009;81: 438-443.
85. Pérez-Armendariz EM, Sáez JC, Bravo-Moreno JF, López-Olmos V, Enders GC, Villalpando I. Connexin43 is expressed in mouse fetal ovary. Anat Rec. 2003;271A:360-367.
86. Ai Z, Fischer A, Spray DC, BrownAM,Fishman GI. Wnt-1 regulation of connexin43 in cardiac myocytes. J Clin Invest. 2000;105:161-171.
87. Sirnes S, Bruun J, Kolberg M, et al. Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer. 2011;131:570-581.
88. Childs AJ, Kinnell HL, Collins CS, et al. BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis. Stem Cells. 2010;28:1368-1378.
89. Huansheng D, Qingjie P, Hanqiong Z, Lianjun Z, Bo C, Wenbin Y. Estrogen inhibits the early development of mouse follicles through regulating the expression of Kit ligand. Biochem Biophys Res Commun. 2011;410:659-664.
90. White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012;18:413-421.
91. Byskov AG, Høyer PE, Yding Andersen C, Kristensen SG, Jespersen A, Möllgård K. No evidence for the presence of oogonia in the human ovary after their final clearance during the first two years of life.HumReprod. 2011;26:2129-2139.
92. Lee PA, Houk CP, Ahmed SF, Hughes IA; International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. Consensus statement on management of intersex disorders. Pediatrics. 2006;118:e488-e500.
93. Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH. Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev. 2006;27:468-484.
94. Stettner AR, Hartenbach EM, Schink JC, et al. Familial ovarian germ cell cancer: Report and review. Am J Med Genet. 1999;84:43-46.
95. Cyriac S, Rajendranath R, Robert LA, Sagar TG. Familial germ cell tumor. Indian J Hum Genet. 2012;18:119-121.
96. Giambartolomei C, Mueller CM, Greene MH, Korde LA. A mini-review of familial ovarian germ cell tumors: an additional manifestation of the familial testicular germ cell tumor syndrome. Cancer Epidemiol. 2009;33:31-36.
97. Kratz CP, Mai PL, Greene MH. Familial testicular germ cell tumours. Best Pract Res Clin Endocrinol. 2010;24: 503-513.
98. Heimdal K, Olsson H, Tretli S, Flodgren P, Borresen AL, Fosså SD. Familial testicular cancer in Norway and southern Sweden. Br J Cancer. 1996;73:964-969.
99. Dong C, Hemminki K. Modification of cancer risks in offspring by sibling and parental cancers from 2,112,616 nuclear families. Int J Cancer. 2001;92:144-150.
100. Dong C, Lönnstedt I, Hemminki K. Familial testicular cancer and second primary cancers in testicular cancer patients by histological type. Eur J Cancer. 2001;37:1878-1885.
101. Czene K, Lichtenstein P, Hemminki K. Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family-cancer database. Int J Cancer. 2002; 99:260-266.
102. Rapley EA, Crockford GP, Teare D, et al. Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours. Nat Genet. 2000;24:197-200.
103. Nathanson KL, Kanetsky PA, Hawes R, et al. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am J Hum Genet. 2005;77:1034-1043.
104. Rapley EA, Turnbull C, Al Olama AA, et al. A genomewide association study of testicular germ cell tumor. Nat Genet. 2009;41:807-810.
105. Kanetsky PA, Mitra N, Vardhanabhuti S, et al. Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet. 2009;41:811-815.
106. Turnbull C, Rapley EA, Seal S, et al. Variants near DMRT1,TERTand ATF7IP are associated with testicular germ cell cancer. Nat Genet. 2010;42:604-607.
107. Kratz CP, Han SS, Rosenberg PS, et al. Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour. J Med Genet. 2011;48:473-476.
108. Poynter JN, Hooten AJ, Lindsay Frazier A, Ross JA. Associations between variants inKITLG,SPRY4,BAK1, and DMRT1 and pediatric germ cell tumors. Genes Chromosome Cancer. 2012;51:266-271.
109. Dalgaard MD, Weinhold N, Edsgärd D, et al. A genomewide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation. J Med Genet. 2012;49:58-65.
110. Chanock S. High marks for GWAS. Nat Genet. 2009;41: 765-766.
111. Kratz CP, Greene MH, Bratslavsky G, Shi J. A stratified genetic risk assessment for testicular cancer. Int J Androl. 2011;34:e98-e102.
112. Stephansson O, Wahnström C, Pettersson A, et al. Perinatal risk factors for childhood testicular germ-cell cancer: a Nordic population-based study. Cancer Epidemiol. 2011; 35:e100-e104.
113. Cook MB, Graubard BI, Rubertone MV, Erickson RL, McGlynn KA. Perinatal factors and the risk of testicular germ cell tumors. Int J Cancer. 2008;122:2600-2606.
114. McGlynn KA, Cook MB. Etiologic factors in testicular germ-cell tumors. Future Oncol. 2009;5:1389-1402.
115. Sharpe RM, Skakkebaek NE. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil Steril. 2008;89:e33-e38.
116. Skakkebæk NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: opinion. Hum Reprod. 2001;16:972-978.
117. Walker AH, Ross RK, Haile RW, Henderson BE. Hormonal factors and risk of ovarian germ cell cancer in young women. Br J Cancer. 1988;57:418-422.
118. Horn-Ross PL, Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: Collaborative analysis of 12 U.S. case-control studies. VI. Nonepithelial cancers among adults. Collaborative Ovarian Cancer Group. Epidemiology. 1992;3:490-495.
119. Adami HO, Lambe M, Persson I, et al. Parity, age at first childbirth, and risk of ovarian cancer. Lancet. 1994;344: 1250-1254.
120. Albrektsen G, Heuch I, Kvåle G. Full-term pregnancies and incidence of ovarian cancer of stromal and germ cell origin: a Norwegian prospective study. Br J Cancer. 1997;75: 767-770.
121. Chen T, Surcel HM, Lundin E, et al. Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2011; 20:324-336.
122. Manikkam M, Guerrero-Bosagna C, Tracey R, Haque MM, Skinner MK. Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures. PLoS One. 2012;7:e31901.
123. Scully RE. Gonadoblastoma.Areview of 74 cases. Cancer. 1970;25:1340-1356.
124. Cools M, Stoop H, Kersemaekers AM, et al. Gonadoblastoma arising in undifferentiated gonadal tissue within dysgenetic gonads. J Clin Endocrinol Metab. 2006;91:2404-2413.
125. Talerman A, Vang R. Germ cell tumors of the ovary. In: Kurman RJ, Ellenson LH, Ronnett BM, eds. Blaustein's Pathology of the Female Genital Tract. New York, NY: Springer; 2011:847-907.
126. Koo YJ, Chun YK, Kwon YS, et al. Ovarian gonadoblastoma with dysgerminoma in a woman with 46XX karyotype. Pathol Int. 2011;61:171-173.
127. Zhao S, Kato N, Endoh Y, Jin Z, Ajioka Y, Motoyama T. Ovarian gonadoblastoma with mixed germ cell tumor in a womanwith 46,XX karyotype and successful pregnancies. Pathol Int. 2000;50:332-335.
128. Shahsiah R, Jahanbin B, Rabiei R, Ardalan FA, Sarhadi B, Izadi-Mood N. Malignant ovarian germ cell tumours in gonadal Y chromosome mosaicism. J Clin Pathol. 2011; 64:973-976.
129. Ledig S, Hiort O, Scherer G, et al. Array-CGH analysis in patients with syndromic and non-syndromic XY gonadal dysgenesis: Evaluation of array CGH as diagnostic tool and search for new candidate loci. Hum Reprod. 2010;25: 2637-2646.
130. Bashamboo A, Ledig S, Wieacker P, Achermann JC, McElreavey K. New technologies for the identification of novel genetic markers of disorders of sex development (DSD). Sex Dev. 2010;4:213-224.
131. Kraggerud SM, Szymanska J, Abeler VM, et al.DNAcopy number changes in malignant ovarian germ cell tumors. Cancer Res. 2000;60:3025-3030.
132. Kildal W, Kraggerud SM, Abeler VM, et al. Genome profiles of bilateral dysgerminomas, a unilateral gonadoblastoma, and a metastasis from a 46,XY phenotypic female. Hum Pathol. 2003;34:946-949.
133. Lee-Jones L, Williams T, Little E, Sampson J. Trisomy 14pter3q21: a case with associated ovarian germ cell tumor and review of the literature. Am J Med Genet. 2004; 128A:78-84.
134. Gimelli S, Beri S, Drabkin HA, et al. The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22)(q24.13;q11.21) in a young girl with dysgerminoma. Mol Cancer. 2009;8:52.
135. Kildal W, Kærn J, Kraggerud SM, et al. Evaluation of genomic changes in a large series of malignant ovarian germ cell tumors-relation to clinicopathologic variables. Cancer Genet Cytogenet. 2004;155:25-32.
136. Silver SA, Wiley JM, Perlman EJ. DNA ploidy analysis of pediatric germ cell tumors. Mod Pathol. 1994;7:951-956.
137. Gibas Z, Talerman A. Analysis of chromosome aneuploidy in ovarian dysgerminoma by flow cytometry and fluorescence in situ hybridization. Diagn Mol Pathol. 1993;2:50-56.
138. Palmquist MB, Webb MJ, Lieber MM, Gaffey TA, Nativ O. DNA ploidy of ovarian dysgerminomas: correlation with clinical outcome. Gynecol Oncol. 1992;44:13-16.
139. Baker BA, Frickey L, Yu IT, Hawkins EP, Cushing B, Perlman EJ. DNA content of ovarian immature teratomas and malignant germ cell tumors. Gynecol Oncol. 1998;71:14-18.
140. Oud PS, Soeters RP, Pahlplatz MM, et al. DNA cytometry of pure dysgerminomas of the ovary. Int J Gynecol Pathol. 1988;7:258-267.
141. Kelley JL, Naus GJ, Christopherson WA. Endodermal sinus tumor of the ovary: a case series with flow cytometric DNA content analysis. Gynecol Oncol. 1991;42:34-38.
142. Kommoss F, Bibbo M, Talerman A. Nuclear deoxyribonucleic acid content (ploidy) of endodermal sinus (yolk sac) tumor. Lab Invest. 1990;62:223-231.
143. Atkin NB. ModalDNAvalue and chromosome number in ovarian neoplasia. A clinical and histopathologic assessment. Cancer. 1971;27:1064-1073.
144. Kihana T, Tsuda H, Teshima S, Okada S, Matsuura S, Hirohashi S. High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumorDNAaneuploidy. Cancer Sci. 1992;83:978-984.
145. Feichter GE, Kühn W, Czernobilsky B, et al. DNA flow cytometry of ovarian tumors with correlation to histopathology. Int J Gynecol Pathol. 1985;4:336-345.
146. Jenderny J, Koster E, Meyer A, et al. Detection of chromosome aberrations in paraffin sections of seven gonadal yolk sac tumors of childhood. Hum Genet. 1995;96:644-650.
147. KühnW, KaufmannM,Feichter GE,RummelHH,Schmid H, Heberling D. DNA flow cytometry, clinical and morphological parameters as prognostic factors for advanced malignant and borderline ovarian tumors. Gynecol Oncol. 1989;33:360-367.
148. Stock C, Ambros IM, Lion T, et al. Detection of numerical and structural chromosome abnormalities in pediatric germ cell tumors by means of interphase cytogenetics. Genes Chromosomes Cancer. 1994;11:40-50.
149. RiopelMA,Spellerberg A, Griffin CA, Perlman EJ. Genetic analysis of ovarian germ cell tumors by comparative genomic hybridization. Cancer Res. 1998;58:3105-3110.
150. Zahn S, Sievers S, Alemazkour K, et al. Imbalances of chromosome arm 1p in pediatric and adult germ cell tumors are caused by true allelic loss: a combined comparative genomic hybridization and microsatellite analysis. Genes Chromosomes Cancer. 2006;45:995-1006.
151. Veltman I, Veltman J, Janssen I, et al. Identification of recurrent chromosomal aberrations in germ cell tumors of neonates and infants using genomewide array-based comparative genomic hybridization. Genes Chromosomes Cancer. 2005;43:367-376.
152. Palmer RD, Foster NA, Vowler SL, et al. Malignant germ cell tumours of childhood: new associations of genomic imbalance. Br J Cancer. 2007;96:667-676.
153. Cheng L, Zhang S, Talerman A, Roth LM. Morphologic, immunohistochemical, and fluorescence in situ hybridization study of ovarian embryonal carcinoma with comparison to solid variant of yolk sac tumor and immature teratoma. Hum Pathol. 2010;41:716-723.
154. Cossu-Rocca P, Zhang S, Roth LM, et al. Chromosome 12p abnormalities in dysgerminoma of the ovary: a FISH analysis. Mod Pathol. 2006;19:611-615.
155. Poulos C, Cheng L, Zhang S, Gersell DJ, Ulbright TM. Analysis of ovarian teratomas for isochromosome 12p: evidence supporting a dual histogenetic pathway for teratomatous elements. Mod Pathol. 2006;19:766-771.
156. Cheng L, Roth LM, Zhang S, et al. KIT gene mutation and amplification in dysgerminoma of the ovary. Cancer. 2011;117:2096-2103.
157. Wehle D, Yonescu R, Long PP, Gala N, Epstein J, Griffin CA. Fluorescence in situ hybridization of 12p in germ cell tumors using a bacterial artificial chromosome clone 12p probe on paraffin-embedded tissue: clinical test validation. Cancer Genet Cytogenet. 2008;183:99-104.
158. Bussey KJ, Lawce HJ, Himoe E, et al. Chromosomes 1 and 12 abnormalities in pediatric germ cell tumors by interphase fluorescence in situ hybridization. Cancer Genet Cytogenet. 2001;125:112-118.
159. Faulkner SW, Friedlander ML. Molecular genetic analysis of malignant ovarian germ cell tumors. Gynecol Oncol. 2000;77:283-288.
160. Faulkner SW, Friedlander ML. Microsatellite instability in germ cell tumors of the testis and ovary. Gynecol Oncol. 2000;79:38-43.
161. Radice P, Pierotti MA, Lacerenza S, et al. Loss of heterozygosity in human germinal tumors. Cytogenet Cell Genet. 1989;52:72-76.
162. King BL, Carcangiu ML, Carter D, et al. Microsatellite instability in ovarian neoplasms. Br J Cancer. 1995;72: 376-382.
163. Okpanyi V, Schneider DT, Zahn S, et al. Analysis of the adenomatous polyposis coli (APC) gene in childhood and adolescent germ cell tumors. Pediatr Blood Cancer. 2011; 56:384-391.
164. FritschMK,Schneider DT, Schuster AE, Murdoch FE, Perlman EJ. Activation of Wnt/β-catenin signaling in distinct histologic subtypes of human germ cell tumors. Pediatr Dev Pathol. 2006;9:115-131.
165. Looijenga LH, Hersmus R, Gillis AJ, et al. Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene. Cancer Res. 2006;66:290-302.
166. Fustino N, Rakheja D, Ateek CS, Neumann JC, Amatruda JF. Bone morphogenetic protein signalling activity distinguishes histological subsets of paediatric germ cell tumours. Int J Androl. 2011;34:e218-e233.
167. Palmer RD, Barbosa-Morais NL, Gooding EL, et al; Children's Cancer and Leukaemia Group. Pediatric malignant germ cell tumors show characteristic transcriptome profiles. Cancer Res. 2008;68:4239-4247.
168. Palmer RD, Murray MJ, Saini HK, et al; Children's Cancer and Leukaemia Group. Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets. Cancer Res. 2010;70:2911-2923.
169. Gillis AJ, Stoop HJ, Hersmus R, et al. High-throughput microRNAome analysis in human germ cell tumours. J Pathol. 2007;213:319-328.
170. Murray M, Saini H, van Dongen S, et al. The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression. Mol Cancer. 2010;9:290.
171. Kawauchi S, Yamamoto Y, Uchida K, et al. Significance of cyclin E and p27 expression in malignant ovarian germ cell tumors: Correlation with the cell proliferation activity and clinicopathologic features. Oncol Rep. 2006;16:1029-1033.
172. Kawauchi S, Liu XP, Kawasaki K, et al. Significance of β-catenin and pRB pathway components in malignant ovarian germ cell tumours: INK4A promoter CpG island methylation is associated with cell proliferation. J Pathol. 2004;204:268-276.
173. Cobellis L, Cataldi P, Reis FM, et al. Gonadal malignant germ cell tumors express immunoreactive inhibin/activin subunits. Eur J Endocrinol. 2001;145:779-784.
174. Tanoguchi K, Sasano H, Yabuki N, et al. Immunohistochemical and two-parameter flow cytometric studies of DNA topoisomerase II alpha in human epithelial ovarian carcinoma and germ cell tumor. Mod Pathol. 1998;11: 186-193.
175. Jin JS, Yao CW, Loh SH, Cheng MF, Hsieh DS, Bai CY. Increasing expression of extracellular matrix metalloprotease inducer in ovary tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters. Int J Gynecol Pathol. 2006;25:140-146.
176. Soini Y, PääkköP. Extent of apoptosis in relation to p53 and bcl-2 expression in germ cell tumors. Hum Pathol. 1996;27:1221-1226.
177. Kemmer K, Corless CL, Fletcher JA, et al. KIT mutations are common in testicular seminomas. Am J Pathol. 2004; 164:305-313.
178. Tian Q, Frierson HF, Krystal GW, Moskaluk CA. Activating c-kit gene mutations in human germ cell tumors. Am J Pathol. 1999;154:1643-1647.
179. Liu FS, Ho ES, Chen JT, Shih RT, Yang CH, Shih A. Overexpression or mutation of the p53 tumor suppressor gene does not occur in malignant ovarian germ cell tumors. Cancer. 1995;76:291-295.
180. Okamoto A, Sameshima Y, Yokoyama S, et al. Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res. 1991;51:5171-5176.
181. Heravi-Moussavi A, Anglesio MS, Cheng SW, et al. Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med. 2011;366:234-242.
182. Ichikawa Y, Yoshida S, Koyama Y, et al. Inactivation of p16/CDKN2 and p15/MTS2 genes in different histological types and clinical stages of primary ovarian tumors. Int J Cancer. 1996;69:466-470.
183. Sievers S, Alemazkour K, Zahn S, et al. IGF2/H19 imprinting analysis of human germ cell tumors (GCTs) using the methylation-sensitive single-nucleotide primer extensionmethod reflects the origin of GCTs in different stages of primordial germ cell development. Genes Chromosomes Cancer. 2005;44:256-264.
184. Schneider DT, Schuster AE, Fritsch MK, et al; Pediatric Oncology Group, German Pediatric Germ Cell Tumor Study Group. Multipoint imprinting analysis indicates a common precursor cell for gonadal and nongonadal pediatric germ cell tumors. Cancer Res. 2001;61:7268-7276.
185. Ross JA, Schmidt PT, Perentesis JP, Davies SM. Genomic imprinting of H19 and insulin-like growth factor-2 in pediatric germ cell tumors. Cancer. 1999;85:1389-1394.
186. Bussey KJ, Lawce HJ, Himoe E, et al. SNRPN methylation patterns in germ cell tumors as a reflection of primordial germ cell development. Genes Chromosomes Cancer. 2001;32:342-352.
187. Jeyapalan JN, Noor DA, Lee SH, et al. Methylator phenotype of malignant germ cell tumours in children identifies strong candidates for chemotherapy resistance. Br J Cancer. 2011;105:575-585.
188. Haider S, Ballester B, Smedley D, Zhang J, Rice P, Kasprzyk A. BioMart Central Portal: unified access to biological data. Nucleic Acids Res. 2009;37:W23-W27.
189. Bruford EA, Lush MJ, Wright MW, Sneddon TP, Povey S, Birney E. TheHGNCDatabase in 2008: a resource for the human genome. Nucleic Acids Res. 2008;36:D445-D448.
190. Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: the human gene integrator. Database. 2010;2010: baq020.
191. Asadourian LA, Taylor HB. Dysgerminoma. An analysis of 105 cases. Obstet Gynecol. 1969;33:370-379.
192. Brassesco MS, Castro-Gamero AM, Valera ET, Neder L, Elias J, Tone LG. 3q27 aberrations in a childhood ovary teratoma with associated malignant germ cell component. Pediatr Blood Cancer. 2009;52:398-401.
193. Atkin NB, Baker MC. i(12p): specific chromosomal marker in seminoma and malignant teratoma of the testis? Cancer Genet Cytogenet. 1983;10:199-204.
194. Alagaratnam S, Lind GE, Kraggerud SM, Lothe RA, Skotheim RI. The testicular germ cell tumour transcriptome. Int J Androl. 2011;34:e133-e151.
195. Skotheim RI, Lind GE, Monni O, et al. Differentiation of human embryonal carcinomas in vitro and in vivo reveals expression profiles relevant to normal development. Cancer Res. 2005;65:5588-5598.
196. Fulda S. Caspase-8 in cancer biology and therapy. Cancer Lett. 2009;281:128-133.
197. Fulton N, Martins da Silva SJ, Bayne RA, Anderson RA. Germ cell proliferation and apoptosis in the developing human ovary. J Clin Endocrinol Metab. 2005;90:4664-4670.
198. Helfer B, Boswell BC, Finlay D, et al. Caspase-8 promotes cell motility and calpain activity under nonapoptotic conditions. Cancer Res. 2006;66:4273-4278.
199. Finlay D, Vuori K. Novel noncatalytic role for caspase-8 in promoting Src-mediated adhesion and Erk signaling in neuroblastoma cells. Cancer Res. 2007;67:11704-11711.
200. Kumper S, Ridley AJ. p120ctn and P-cadherin but not Ecadherin regulate cell motility and invasion of DU145 prostate cancer cells. PLoS One. 2010;5:e11801.
201. Turashvili G, McKinney SE, Goktepe O, et al. P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer. Mod Pathol. 2011;24: 64-81.
202. Bendel-Stenzel MR, Gomperts M, Anderson R, Heasman J, Wylie C. The role of cadherins during primordial germ cell migration and early gonad formation in the mouse. Mech Dev. 2000;91:143-152.
203. Grivennikov S, Karin M. Autocrine IL-6 signaling: a key event in tumorigenesis? Cancer Cell. 2008;13:7-9.
204. Eddie SL, Childs AJ, Jabbour HN, Anderson RA. Developmentally regulated IL6-type cytokines signal to germ cells in the human fetal ovary. Mol Hum Reprod. 2012; 18:88-95.
205. Chuma S, Nakatsuji N. Autonomous transition into meiosis of mouse fetal germ cells in vitro and its inhibition by gp130-mediated signaling. Dev Biol. 2001;229:468-479.
206. Schweyer S, Soruri A, Baumhoer D, et al. Expression of CXC chemokine IP-10 in testicular germ cell tumours. J Pathol. 2002;197:89-97.
207. Dietl J, Horny HP, Ruck P, Kaiserling E. Dysgerminoma of the ovary. An immunohistochemical study of tumor-infiltrating lymphoreticular cells and tumor cells. Cancer. 1993;71:2562-2568.
208. Sasada T, Suekane S. Variation of tumor-infiltrating lymphocytes in human cancers: controversy on clinical significance. Immunotherapy. 2011;3:1235-1251.
209. Ben-Baruch A. The multifaceted roles of chemokines in malignancy. Cancer Metastasis Rev. 2006;25:357-371.
210. Belperio JA, Keane MP, Arenberg DA, et al. CXC chemokines in angiogenesis. J Leukocyte Biol. 2000;68:1-8.
211. Panagopoulos I, Moller E, Collin A, Mertens F. The POU5F1P1 pseudogene encodes a putative protein similar to POU5F1 isoform 1. Oncol Rep. 2008;20:1029-1033.
212. Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G. Tumor invasion in the absence of epithelialmesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell. 2006;9:261-272.
213. Rider CC, Mulloy B. Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists. Biochem J. 2010;429:1-12.
214. Neumann JC, Chandler GL, Damoulis VA, et al. Mutation in the type IB bone morphogenetic protein receptor alk6b impairs germ-cell differentiation and causes germ-cell tumors in zebrafish. Proc Natl Acad Sci U S A. 2011;108: 13153-13158.
215. Alves Vidigal J, Ventura A. Embryonic stem cell miRNAs and their roles in development and disease. Semin Cancer Biol. 2012;22:428-436.
216. Zhou AD, Diao LT, Xu H, et al. β-Catenin/LEF1 transactivates the microRNA-371-373 cluster that modulates the Wnt/β-catenin-signaling pathway. Oncogene. 2011; 31:2968-2978.
217. Loayza-Puch F, Yoshida Y, Matsuzaki T, Takahashi C, Kitayama H, Noda M. Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs. Oncogene. 2010;29:2638-2648.
218. Harris T, Jimenez L, Kawachi N, et al. Low-level expression of miR-375 correlates with poor outcome and metastasis while altering the invasive properties of head and necksquamous cell carcinomas. Am J Pathol. 2012;180:917-928.
219. Zhang X, Yan Z, Zhang J, et al. Combination of hsa-miR-375 and hsa-miR-142-5p as a predictor for recurrence risk in gastric cancer patients following surgical resection. Ann Oncol. 2011;22:2257-2266.
220. Kong KL, Kwong DL, Chan TH, et al. MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut. 2012;61:33-42.
221. Yu L, Todd NW, Xing L, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer. 2010;127:2870-2878.
222. Bryant RJ, Pawlowski T, Catto JW, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer. 2012;106:768-774.
223. Murray MJ, Halsall DJ, Hook CE, Williams DM, Nicholson JC, Coleman N. Identification of microRNAs from the miR-371β373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors. Am J Clin Pathol. 2011;135:119-125.
224. Lipchina I, Elkabetz Y, Hafner M, et al. Genome-wide identification of microRNA targets in human ES cells reveals a role for miR-302 in modulating BMP response. Gene Dev. 2011;25:2173-2186.
225. Garcia AI, Buisson M, Bertrand P, et al. Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med. 2011;3:279-290.
226. Faraoni I, Antonetti FR, Cardone J, Bonmassar E. miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta. 2009;1792:497-505.
227. Sarver A, French A, Borralho P, et al. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer. 2009;9: 401.
228. Chang S, Wang RH, Akagi K, et al. Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155. Nat Med. 2011;17:1275-1282.
229. Moskwa P, Buffa FM, Pan Y, et al. miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell. 2011;41:210-220.
230. Valeri N, Gasparini P, Fabbri M, et al. Modulation of mismatch repair and genomic stability by miR-155. Proc Natl Acad Sci U S A. 2010;107:6982-6987.
231. Tili E, Michaille JJ, Wernicke D, et al. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc Natl Acad Sci U S A. 2011;108:4908-4913.
232. Cekaite L, Rantala J, Bruun J, et al. MicroRNAs miR-9,-31, and-182 are implicated in cell proliferation and apoptosis in colon cancer. Neoplasia. 2012;14:838-879.
233. Ormestad M, Astorga J, Landgren H, et al. Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production. Development. 2006;133:833-843.
234. Yu Z, Raabe T, Hecht NB. MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell transition protein 2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage. Biol Reprod. 2005;73:427-433.
235. Buchold GM, Coarfa C, Kim J, Milosavljevic A, Gunaratne PH, Matzuk MM. Analysis of microRNA expression in the prepubertal testis. PLoS One. 2010;5:e15317.
236. Burns DM, D'Ambrogio A, Nottrott S, Richter JD. CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation. Nature. 2011;473:105-108.
237. Gregory PA, Bracken CP, Smith E, et al.AnautocrineTGF-β/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol Biol Cell. 2011;22:1686-1698.
238. Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 2009;8:843-852.
239. Knouf EC, Garg K, Arroyo JD, et al. An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription. Nucleic Acids Res. 2012;40:499-510.
240. Yao Y, Suo AL, Li ZF, et al. MicroRNA profiling of human gastric cancer. Mol Med Report. 2009;2:963-970.
241. Kahlert C, Klupp F, Brand K, et al. Invasion front-specific expression and prognostic significance of microRNA in colorectal liver metastases. Cancer Sci. 2011;102:1799-1807.
242. Li D, Wang Q, Liu C, et al. Aberrant expression of miR-638 contributes to benzo(a)pyrene-induced human cell transformation. Toxicol Sci. 2012;125:382-391.
243. Gilbert D, Rapley E, Shipley J. Testicular germ cell tumours: predisposition genes and the male germ cell niche. Nat Rev Cancer. 2011;11:278-288.
244. Salonen J, Leminen A, Stenman UH, Bützow R, Heikinheimo M, Heikinheimo O. Tissue AP-2g and Oct-3/4, and serum CA 125 as diagnostic and prognostic markers of malignant ovarian germ cell tumors. Tumor Biol. 2008; 29:50-56.
245. Pauls K, Jäger R, Weber S, et al. Transcription factor AP-2g, a novel marker of gonocytes and seminomatous germ cell tumors. Int J Cancer. 2005;115:470-477.
246. Wang L, Chang X, Yuan G, Zhao Y, Wang P. Expression of peptidylarginine deiminase type 4 in ovarian tumors. Int J Biol Sci. 2010;6:454-464.
247. Soini Y, Talvensaari-Mattila A. Expression of claudins 1, 4, 5, and 7 in ovarian tumors of diverse types. Int J Gynecol Pathol. 2006;25:330-335.
248. Salonen J, Butzow R, Palvimo JJ, Heikinheimo M, Heikinheimo O. Oestrogen receptors and small nuclear ring finger protein 4 (RNF4) in malignant ovarian germ cell tumours. Mol Cell Endocrinol. 2009;307:205-210.
249. Bing Z, Pasha TL, Lal P, Tomaszewski JE. Expression of glial cell line-derived neurotropic factor receptor a-1 in immature teratomas. Am J Clin Pathol. 2008;130:892-896.
250. Kohno Y, Matsuki Y, Tanimoto A, et al. Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen. Br J Cancer. 2006;94:710-716.
251. West JA, Viswanathan SR, Yabuuchi A, et al. A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature. 2009;460:909-913.
252. Xue D, Peng Y, Wang F, Allan RW, Cao D. RNA-binding protein LIN28 is a sensitive marker of ovarian primitive germ cell tumours. Histopathology. 2011;59:452-459.
253. Palma I, Peña RY, Contreras A, et al. Participation ofOCT3/4 and β-catenin during dysgenetic gonadal malignant transformation. Cancer Lett. 2008;263:204-211.
254. Cheng L, Thomas A, Roth LM, Zheng W, Michael H, KarimFW.OCT4:a novel biomarker for dysgerminoma of the ovary. Am J Surg Pathol. 2004;28:1341-1346.
255. ChangMC, Vargas SO, Hornick JL, Hirsch MS, Crum CP, Nucci MR. Embryonic stem cell transcription factors and D2-40 (podoplanin) as diagnostic immunohistochemical markers in ovarian germ cell tumors. Int J Gynecol Pathol. 2009;28:347-355.
256. Abiko K, Mandai M, Hamanishi J, et al. Oct4 expression in immature teratoma of the ovary: relevance to histologic grade and degree of differentiation. Am J Surg Pathol. 2010;34:1842-1848.
257. Chambers I, Tomlinson SR. The transcriptional foundation of pluripotency. Development. 2009;136:2311-2322.
258. PerrettRM,Turnpenny L, Eckert JJ, et al. The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture. Biol Reprod. 2008; 78:852-858.
259. Weber S, Eckert D, Nettersheim D, et al. Critical function of AP-2γ/TCFAP2C in mouse embryonic germ cell maintenance. Biol Reprod. 2010;82:214-223.
260. Huang S, Jean D, Luca M, Tainsky MA, Bar-Eli M. Loss of AP-2 results in downregulation of c-KIT and enhancement of melanoma tumorigenicity and metastasis. EMBO J. 1998;17:4358-4369.
261. Sartini S, Dario B, MorelliM,DaSF, La Motta C. Receptor tyrosine kinase kit and gastrointestinal stromal tumours: an overview. Curr Med Chem. 2011;18:2893-2903.
262. Renneville A, Roumier C, Biggio V, et al. Cooperating gene mutations in acute myeloid leukemia: a review of the literature. Leukemia. 2008;22:915-931.
263. Rajpert-De Meyts E, Skakkebaek NE. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours. Int J Androl. 1994;17:85-92.
264. Ramalingam P, Malpica A, Silva EG, Gershenson DM, Liu JL, Deavers MT. The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from endometrioid and clear cell carcinomas. Am J Surg Pathol. 2004;28: 499-505.
265. Inoue M, Kyo S, Fujita M, Enomoto T, Kondoh G. Coexpression of the c-kit receptor and the stem cell factor in gynecological tumors. Cancer Res. 1994;54:3049-3053.
266. Tsuura Y, Hiraki H, Watanabe K, et al. Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed, paraffin-embedded tissues. Virchows Arch. 1994;424:135-141.
267. Went PT, Dirnhofer S, Bundi M, et al. Prevalence of KIT expression in human tumors. J Clin Oncol. 2004;22: 4514-4522.
268. Sever M, Jones TD, Roth LM, et al. Expression of CD117 (c-kit) receptor in dysgerminoma of the ovary: diagnostic and therapeutic implications.ModPathol. 2005;18:1411-1416.
269. Masson K, Rönnstrand L. Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3. Cell Signal. 2009;21:1717-1726.
270. Pauls K, Wardelmann E, Merkelbach-Bruse S, Büttner R, Zhou H. c-KIT codon 816 mutation in a recurrent and metastatic dysgerminoma of a 14-year-old girl: Case study. Virchows Arch. 2004;445:651-654.
271. Heinrich MC, Blanke CD, Druker BJ, Corless CL. Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol. 2002;20:1692-1703.
272. Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011;11:865-878.
273. Eiring A, Khorashad J, Morley K, Deininger M. Advances in the treatment of chronic myeloid leukemia. BMC Med. 2011;9:99.
274. Fleischer RT, Vollenhoven BJ, Weston GC. The effects of chemotherapy and radiotherapy on fertility in premenopausal women. Obstet Gynecol Surv. 2011;66:248-254.
275. Pedersini R, Vattemi E, Mazzoleni G, Graiff C. Complete response after treatment with imatinib in pretreated disseminated testicular seminoma with overexpression of c-KIT. Lancet Oncol. 2007;8:1039-1040.
276. Pectasides D, Nikolaou M, Pectasides E, Koumarianou A, Valavanis C, Economopoulos T. Complete response after imatinib mesylate administration in a patient with chemoresistant stage IV seminoma. Anticancer Res. 2008; 28:2317-2320.
277. Einhorn LH, Brames MJ, Heinrich MC, Corless CL, Madani A. Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT. Am J Clin Oncol. 2006;29:12-13.
278. Schacht V, Dadras SS, Johnson LA, JacksonDG,HongYK, Detmar M. Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors.AmJ Pathol. 2005;166:913-921.
279. Sonne S, Herlihy A, Hoei-Hansen CE, et al. Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours. Virchows Arch. 2006;449: 200-206.
280. Stenning SP, Parkinson MC, Fisher C, et al. Postchemotherapy residual masses in germ cell tumor patients. Cancer. 1998;83:1409-1419.
281. Palmer PE, Wolfe HJ. Immunocytochemical localization of oncodevelopmental proteins in human germ cell and hepatic tumors. J Histochem Cytochem. 1978;26:523-531.
282. Siltanen S, Anttonen M, HeikkiläP, et al. Transcription factor GATA-4 is expressed in pediatric yolk sac tumors. Am J Pathol. 1999;155:1823-1829.
283. Esheba GE, Pate LL, Longacre TA. Oncofetal protein glypican-3 distinguishes yolk sac tumor from clear cell carcinoma of the ovary.AmJ Surg Pathol. 2008;32:600-607.
284. Siltanen S, HeikkiläP, Bielinska M, Wilson DB, Heikinheimo M. Transcription factor GATA-6 is expressed in malignant endoderm of pediatric yolk sac tumors and in teratomas. Pediatr Res. 2003;54:542-546.
285. Mannisto S, Butzow R, Salonen J, Leminen A, Heikinheimo O, Heikinheimo M. Transcription factors GATA-4 and GATA-6, and their potential downstream effectors in ovarian germ cell tumors. Tumor Biol. 2005;26:265-273.
286. Zynger DL, Everton MJ, Dimov ND, Chou PM, Yang XJ.Expression of glypican 3 in ovarian and extragonadal germ cell tumors. Am J Clin Pathol. 2008;130:224-230.
287. Zynger DL, McCallum JC, Luan C, Chou PM, Yang XJ. Glypican 3 has a higher sensitivity than α-fetoprotein for testicular and ovarian yolk sac tumour: immunohistochemical investigation with analysis of histological growth patterns. Histopathology. 2010;56:750-757.
288. Preda O, Nicolae A, Aneiros-Fernández J, Borda A, Nogales FF. Glypican 3 is a sensitive, but not a specific, marker for the diagnosis of yolk sac tumours. Histopathology. 2011;58:312-314.
289. Hippo Y, Watanabe K, Watanabe A, et al. Identification of solubleNH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res. 2004;64:2418-2423.
290. Hanigan MH, Frierson HF Jr, Abeler VM, Kaern J, Taylor PTJr.Humangerm cell tumours: Expression ofγ-glutamyl transpeptidase and sensitivity to cisplatin. Br J Cancer. 1999;81:75-79.
291. Cossu-Rocca P, Jones TD, RothLM,et al. Cytokeratin and CD30 expression in dysgerminoma. Hum Pathol. 2006; 37:1015-1021.
292. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991;253:49-53.
293. Ye DW, Zheng J, Qian SX, et al. p53 gene mutations in Chinese human testicular seminoma. J Urol. 1993;150: 884-886.
294. Fleischhacker M, Strohmeyer T, Imai Y, Slamon DJ, Koeffler HP. Mutations of the p53 gene are not detectable in human testicular tumors. Mod Pathol. 1994;7:435-439.
295. Schenkman NS, Sesterhenn IA,WAL, et al. Increased p53 protein does not correlate to p53 gene mutations in microdissected human testicular germ cell tumors. J Urol. 1995;154:617-621.
296. Lothe RA, Peltomaki P, Tommerup N, et al. Molecular genetic changes in human male germ cell tumors. Lab Invest. 1995;73:606-614.
297. Guillou L, Estreicher A, Chaubert P, et al.Germcell tumors of the testis overexpress wild-type p53.AmJ Pathol. 1996; 149:1221-1228.
298. Ehteshami M, Ro J, Shin H, Lee J, Ordonez N, Ayala A. p53 expression and tumor proliferative activity in testicular germ-cell tumors. Int J Oncol. 1996;9:787-793.
299. Dietl J, Horny HP, Kaiserling E. Frequent overexpression of p53 in dysgerminoma of the ovary. Gynecol Obstet Invest. 1994;37:141-142.
300. Marx L, Dietl J, Horny HP. Overexpression or mutation of the p53 tumor suppressor gene does not occur in malignant ovarian germ cell tumors. Cancer. 1996;78:179-180.
301. Hu W, Zheng T, Wang J. Regulation of fertility by the p53 family members. Genes Cancer. 2011;2:420-430.
302. Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. The p53 family: Guardians of maternal reproduction. Nat Rev Mol Cell Biol. 2011;12:259-265.
303. Suh EK, Yang A, Kettenbach A, et al. p63 protects the female germ line during meiotic arrest. Nature. 2006;444: 624-628.
304. Crum CP, McKeon FD. p63 in epithelial survival, germ cell surveillance, and neoplasia. Annu Rev Pathol Mech Dis. 2010;5:349-371.
305. Ince TA, Cviko AP, Quade BJ, et al. p63 coordinates anogenital modeling and epithelial cell differentiation in the developing female urogenital tract. Am J Pathol. 2002; 161:1111-1117.
306. Slade I, Bacchelli C, Davies H, et al. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet. 2011;48:273-278.
307. Menezes R, Boetzer M, Sieswerda M, van Ommen GJ, Boer J. Integrated analysis of DNA copy number and gene expression microarray data using gene sets. BMC Bioinformatics. 2009;10:203.
308. Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol. 2005;18:S61-S79.
309. Kraggerud SM, Skotheim RI, Szymanska J, et al. Genome profiles of familial/bilateral and sporadic testicular germ cell tumors. Genes Chromosomes Cancer. 2002;34:168-174.
310. Ihara T, Ohama K, Satoh H, Fujii T, Nomura K, Fujiwara A. Histologic grade and karyotype of immature teratoma of the ovary. Cancer. 1984;54:2988-2994.
311. Vakiani E, Solit DB. KRAS and BRAF: drug targets and predictive biomarkers. J Pathol. 2011;223:220-230.
312. Katoh Y, Katoh M. Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med. 2009;9:873-886.
313. Salonen J, Rajpert-De Meyts E, Mannisto S, et al. Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors. Eur J Endocrinol. 2010;162:625-631.
314. Biermann K, Göke F, Nettersheim D, et al. c-KIT is frequently mutated in bilateral germ cell tumours and downregulated during progression from intratubular germ cell neoplasia to seminoma. J Pathol. 2007;213:311-318.
315. Looijenga LH, de Leeuw H, van Oorschot M, et al. Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors. Cancer Res. 2003;63:7674-7678.
316. Sakuma Y, Matsukuma S, Yoshihara M, et al. Mutations of c-kit gene in bilateral testicular germ cell tumours in Japan. Cancer Lett. 2008;259:119-126.
317. Coffey J, Linger R, Pugh J, et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: Report of 220 tumors and review of literature. Genes Chromosomes Cancer. 2008;47:34-42.
318. Okada K, Katagiri T, Tsunoda T, et al. Analysis of geneexpression profiles in testicular seminomas using a genome-wide cDNA microarray. Int J Oncol. 2003;23: 1615-1635.
319. Skotheim RI, Monni O, Mousses S, et al. New insights into testicular germ cell tumorigenesis from gene expression profiling. Cancer Res. 2002;62:2359-2364.
320. Yamada S, Kohu K, Ishii T, et al. Gene expression profiling identifies a set of transcripts that are up-regulated in human testicular seminoma. DNA Res. 2004;11:335-344.
321. Gashaw I, Grümmer R, Klein-Hitpass L, et al. Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4. CellMolLife Sci. 2005;62:2359-2368.
322. Port M, Schmelz HU, Stockinger M, et al. Gene expression profiling in seminoma and nonseminoma. J Clin Oncol. 2005;23:58-69.
323. Cotterman R, Knoepfler PS. N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28b. PLoS One. 2009;4:e5799.
324. Helland Å, Anglesio MS, George J, et al. Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. PLoS One. 2011;6:e18064.
325. Kumar R, Gururaj AE, Barnes CJ. p21-activated kinases in cancer. Nat Rev Cancer. 2006;6:459-471.
326. Banerjee M, Worth D, ProwseDM,Nikolic M. Pak1 phosphorylation on T212 affects microtubules in cells undergoing mitosis. Curr Biol. 2002;12:1233-1239.
327. Phang JM, Liu W, Zabirnyk O. Proline metabolism and microenvironmental stress.AnnuRev Nutr. 2010;30:441-463.
328. Juric D, Sale S,HromasRA,et al.Gene expression profiling differentiates germ cell tumors from other cancers and defines subtype-specific signatures. Proc Natl Acad SciUSA. 2005;102:17763-17768.
329. Korkola JE, Houldsworth J, Dobrzynski D, et al. Gene expression-based classification of nonseminomatous male germ cell tumors. Oncogene. 2005;24:5101-5107.
330. Korkola JE, Heck S, Olshen AB, et al. In vivo differentiation and genomic evolution in adult male germ cell tumors. Genes Chromosomes Cancer. 2008;47:43-55.
331. Bourdon V, Naef F,RaoPH, et al. Genomic and expression analysis of the 12p11-p12 amplicon usingESTarrays identifies two novel amplified and overexpressed genes. Cancer Res. 2002;62:6218-6223.
332. Rodriguez S, Jafer O, Goker H, et al. Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1. Oncogene. 2003;22:1880-1891.
333. Skotheim RI, Autio R, Lind GE, et al. Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. Cell Oncol. 2006;28: 315-326.
334. Biermann K, Heukamp LC, Steger K, et al. Gene expression profiling identifies new biological markers of neoplastic germ cells. Anticancer Res. 2007;27:3091-3100.
335. McIntyre A, Summersgill B, Lu YJ, et al. Genomic copy number and expression patterns in testicular germ cell tumours. Br J Cancer. 2007;97:1707-1712.
336. Malliri A, Collard JG. Role of Rho-family proteins in cell adhesion and cancer. Curr Opin Cell Biol. 2003;15:583-589.
337. Xu H, Kardash E, Chen S, Raz E, Lin F. Gbg signaling controls the polarization of zebrafish primordial germ cells by regulating Rac activity. Development. 2012; 139:57-62.
338. Jørgensen N,Müller J, Jaubert F, Clausen OP, Skakkebaek NE. Heterogeneity of gonadoblastoma germ cells: similarities with immature germ cells, spermatogonia and testicular carcinoma in situ cells. Histopathology. 1997;30: 177-186.
339. Kasinski AL, Slack FJ. MicroRNAs en route to the clinic: Progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11:849-864.
340. Schneider DT, Schuster AE, Fritsch MK, et al. Genetic analysis of childhood germ cell tumors with comparative genomic hybridization. Klin Padiatr. 2001;213:204-211.
341. He L, Ding H, Wang JH, et al. Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis. PLoS One. 2012;7:e42992.
342. Hersmus R, Stoop H, van de Geijn GJ, et al. Prevalence of c-KIT mutations in gonadoblastoma and dysgerminomas of patients with disorders of sex development (DSD) and ovarian dysgerminomas. PLoS One. 2012;7:e43952.
343. Malecki M, Anderson M, Beauchaine M, Seo S, Tambokan X. TRA-1-60(+), SSEA-4(+), Oct4A(+), Nanog(+) clones of pluripotent stem cells in the embryonal carcinomas of the ovaries. J Stem Cell Res Ther. 2012;2:130.
344. Pauniaho SL, Salonen J, Helminen M, Vettenranta K, Heikinheimo M, Heikinheimo O. The incidences of malignant gonadal and extragonadal germ cell tumors in males and females: a population-based study covering over 40 years in Finland. Cancer Causes Control. 2012; 23:1921-1927.