The differential diagnosis of familial lentiginosis syndromes

Familial Cancer

Volumn 10, Issue 3, 2011, Pages 481-490

  Lodish, Maya B ^a   Stratakis, Constantine A ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

Hamartoma; Lentigines; Mamallian target of rapamycin; Tumor suppressor

Indexed keywords

EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; RAPAMYCIN; SORAFENIB; TEMSIROLIMUS;

BANNAYAN ZONNANA SYNDROME; CARNEY COMPLEX; CLINICAL FEATURE; CONFERENCE PAPER; COWDEN SYNDROME; DIFFERENTIAL DIAGNOSIS; FAMILIAL CANCER; GENETIC COUNSELING; HUMAN; LAUGIER HUNZIKER SYNDROME; LENTIGINOSIS; LEOPARD SYNDROME; NOONAN SYNDROME; PEUTZ JEGHERS SYNDROME; PRIORITY JOURNAL; PTEN HAMARTOMATOUS SYNDROME;

DIAGNOSIS, DIFFERENTIAL; HUMANS; LENTIGO; PEUTZ-JEGHERS SYNDROME;

EID: 80054967568     PISSN: 13899600     EISSN: 15737292     Source Type: Journal    
DOI: 10.1007/s10689-011-9446-x     Document Type: Conference Paper

References (97)

1. Fitzpatrick TB, Wolff K (2008) Fitzpatrick's dermatology in general medicine, 7th edn. McGraw-Hill, New York
2. DJ Marsh CA Stratakis 2001 Hamartoma and lentiginosis syndromes: clinical and molecular aspects Front Horm Res 28 167 213 11443851 10.1159/000061045 1:CAS:528:DC%2BD38XjsVKhsr0%3D (Pubitemid 33816386)
3. CA Stratakis 2000 Genetics of Peutz-Jeghers syndrome, Carney complex and other familial lentiginoses Horm Res 54 334 343 11595829 10.1159/000053283 1:CAS:528:DC%2BD3MXnsVemtLk%3D (Pubitemid 34701745)
4. AJ Bauer CA Stratakis 2005 The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis J Med Genet 42 801 810 15958502 10.1136/jmg.2003.017806 1:CAS:528:DC%2BD2MXht1KrtbbP (Pubitemid 41598187)
5. JLA Peutz 1921 Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. (Dutch) Nederl Maandschr Geneesk 10 134 146
6. Jeghers H, McKusick V, Katz KH (1949) Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance. N Engl J Med 241:993, illust; passim
7. N Hearle V Schumacher FH Menko, et al. 2006 Frequency and spectrum of cancers in the Peutz-Jeghers syndrome Clin Cancer Res 12 3209 3215 16707622 10.1158/1078-0432.CCR-06-0083 1:CAS:528:DC%2BD28Xks1Chsrk%3D (Pubitemid 43837371)
8. CA Stratakis 2000 Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes Front Biosci 5 D353 D366 10704431 10.2741/Stratakis 1:CAS:528:DC%2BD3cXht1Shtbw%3D
9. S Yalcin E Kirli AO Ciftci, et al. 2011 The association of adrenocortical carcinoma and thyroid cancer in a child with Peutz-Jeghers syndrome J Pediatr Surg 46 570 573 21376213 10.1016/j.jpedsurg.2011.01.005
10. L Zirilli P Benatti S Romano, et al. 2009 Differentiated thyroid carcinoma (DTC) in a young woman with Peutz-Jeghers syndrome: are these two conditions associated? Exp Clin Endocrinol Diabetes 117 234 239 19235129 10.1055/s-0028-1102920 1:CAS:528:DC%2BD1MXosl2kt7g%3D
11. M Yamamoto H Hoshino T Onizuka M Ichikawa A Kawakubo S Hayakawa 1992 Thyroid papillary adenocarcinoma in a woman with Peutz-Jeghers syndrome Intern Med 31 1117 1119 1421720 10.2169/internalmedicine.31.1117 1:STN:280: DyaK3s%2FktlOqtQ%3D%3D
12. IP Tomlinson RS Houlston 1997 Peutz-Jeghers syndrome J Med Genet 34 1007 1011 9429144 10.1136/jmg.34.12.1007 1:STN:280:DyaK1c%2FptVynsA%3D%3D (Pubitemid 27522107)
13. LA Boardman FJ Couch LJ Burgart, et al. 2000 Genetic heterogeneity in Peutz-Jeghers syndrome Hum Mutat 16 23 30 10874301 10.1002/1098-1004(200007)16: 1<23::AID-HUMU5>3.0.CO;2-M 1:CAS:528:DC%2BD3cXlsF2htLg%3D (Pubitemid 30447964)
14. SS Wong S Rajakulendran 1996 Peutz-Jeghers syndrome associated with primary malignant melanoma of the rectum Br J Dermatol 135 439 442 8949440 10.1111/j.1365-2133.1996.tb01510.x 1:STN:280:DyaK2s7gs1KqsA%3D%3D (Pubitemid 26297842)
15. M Braitman 1979 Subungual malignant melanoma Cutis 23 617 623 456029 1:STN:280:DyaE1M3ht1CmsA%3D%3D (Pubitemid 9167851)
16. A Rowan V Bataille R MacKie, et al. 1999 Somatic mutations in the Peutz-Jeghers (LKB1/STKII) gene in sporadic malignant melanomas J Invest Dermatol 112 509 511 10201537 10.1046/j.1523-1747.1999.00551.x 1:CAS:528:DyaK1MXit1Ojt7c%3D (Pubitemid 29171943)
17. van Lier MG, Wagner A, Mathus-Vliegen EM, Kuipers EJ, Steyerberg EW, van Leerdam ME (2010) High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol 105:1258-1264; author reply 65
18. SM DePadova-Elder SS Milgraum 1994 Q-switched ruby laser treatment of labial lentigines in Peutz-Jeghers syndrome J Dermatol Surg Oncol 20 830 832 7798417 1:STN:280:DyaK2M%2Fps1aqtg%3D%3D
19. SB Mallory 1987 Stough DBt. genodermatoses with malignant potential Dermatol Clin 5 221 230 3549077 1:STN:280:DyaL2s7mtVWgtQ%3D%3D (Pubitemid 17021251)
20. A Hemminki 1999 The molecular basis and clinical aspects of Peutz-Jeghers syndrome Cell Mol Life Sci 55 735 750 10379360 10.1007/s000180050329 1:CAS:528:DyaK1MXjvVyksL0%3D (Pubitemid 29257624)
21. DE Jenne H Reimann J Nezu, et al. 1998 Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase Nat Genet 18 38 43 9425897 10.1038/ng0198-38 1:CAS:528:DyaK1cXivFelsw%3D%3D (Pubitemid 28027876)
22. A Hemminki D Markie I Tomlinson, et al. 1998 A serine/threonine kinase gene defective in Peutz-Jeghers syndrome Nature 391 184 187 9428765 10.1038/34432 1:CAS:528:DyaK1cXmt1Kjtw%3D%3D (Pubitemid 28092478)
23. N Hearle A Lucassen R Wang, et al. 2004 Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11-negative PJS cases Genes Chromosom Cancer 41 163 169 15287029 10.1002/gcc.20067 1:CAS:528:DC%2BD2cXnslWlu7s%3D (Pubitemid 39096742)
24. P Alhopuro D Phichith S Tuupanen, et al. 2008 Unregulated smooth-muscle myosin in human intestinal neoplasia Proc Natl Acad Sci USA 105 5513 5518 18391202 10.1073/pnas.0801213105 1:CAS:528:DC%2BD1cXkslSntr4%3D (Pubitemid 351753894)
25. H Mehenni C Gehrig J Nezu, et al. 1998 Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity Am J Hum Genet 63 1641 1650 9837816 10.1086/302159 1:CAS:528:DyaK1MXltF2qtg%3D%3D (Pubitemid 30415726)
26. M Miyaki T Iijima K Hosono, et al. 2000 Somatic mutations of LKB1 and beta-catenin genes in gastrointestinal polyps from patients with Peutz-Jeghers syndrome Cancer Res 60 6311 6313 11103790 1:CAS:528:DC%2BD3cXos1Sktro%3D
27. LA Boardman SN Thibodeau DJ Schaid, et al. 1998 Increased risk for cancer in patients with the Peutz-Jeghers syndrome Ann Intern Med 128 896 899 9634427 1:STN:280:DyaK1c3osFegsA%3D%3D (Pubitemid 28289483)
28. KM Zbuk C Eng 2007 Hamartomatous polyposis syndromes Nat Clin Pract Gastroenterol Hepatol 4 492 502 17768394 10.1038/ncpgasthep0902 1:CAS:528:DC%2BD2sXpvFWrsbY%3D (Pubitemid 47371630)
29. Kwiatkowski DJ, Manning BD (2005) Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 14 Spec No. 2:R251-R258 (Pubitemid 41631882)
30. M Rosner M Hanneder N Siegel A Valli C Fuchs M Hengstschlager 2008 The mTOR pathway and its role in human genetic diseases Mutat Res 659 284 292 18598780 10.1016/j.mrrev.2008.06.001 1:CAS:528:DC%2BD1cXhtVKiur%2FM
31. DK Sandsmark C Pelletier JD Weber DH Gutmann 2007 Mammalian target of rapamycin: master regulator of cell growth in the nervous system Histol Histopathol 22 895 903 17503347 1:CAS:528:DC%2BD2sXps1ahsbo%3D (Pubitemid 47034156)
32. JA Carney H Gordon PC Carpenter BV Shenoy VL Go 1985 The complex of myxomas, spotty pigmentation, and endocrine overactivity Medicine (Baltimore) 64 270 283 1:STN:280:DyaL2M3jvFyguw%3D%3D (Pubitemid 16247109)
33. JA Carney LS Hruska GD Beauchamp H Gordon 1986 Dominant inheritance of the complex of myxomas, spotty pigmentation, and endocrine overactivity Mayo Clin Proc 61 165 172 3945116 1:STN:280:DyaL287hslSmug%3D%3D (Pubitemid 16082927)
34. GP Chrousos CA Stratakis 1998 Carney complex and the familial lentiginosis syndromes: link to inherited neoplasias and developmental disorders, and genetic loci J Intern Med 243 573 579 9681861 10.1046/j.1365-2796.1998.00341.x 1:CAS:528:DyaK1cXks1Wkurc%3D (Pubitemid 28312259)
35. CA Stratakis LS Kirschner JA Carney 2001 Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation J Clin Endocrinol Metab 86 4041 4046 11549623 10.1210/jc.86.9.4041 1:CAS:528:DC%2BD3MXmvFCktrk%3D (Pubitemid 32848510)
36. CA Stratakis JA Carney JP Lin, et al. 1996 Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2 J Clin Invest 97 699 705 8609225 10.1172/JCI118467 1:CAS:528:DyaK28XhvVOktbk%3D (Pubitemid 26057088)
37. A Premkumar CA Stratakis TH Shawker DA Papanicolaou GP Chrousos 1997 Testicular ultrasound in Carney complex: report of three cases J Clin Ultrasound 25 211 214 9142622 10.1002/(SICI)1097-0096(199705)25:4<211::AID-JCU10>3. 0.CO;2-N 1:STN:280:DyaK2s3oslGgsg%3D%3D (Pubitemid 27194554)
38. CA Stratakis NA Courcoutsakis A Abati, et al. 1997 Thyroid gland abnormalities in patients with the syndrome of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas (Carney complex) J Clin Endocrinol Metab 82 2037 2043 9215269 10.1210/jc.82.7.2037 1:CAS:528: DyaK2sXksVeqs7g%3D (Pubitemid 27287558)
39. J Bertherat 2006 Carney complex (CNC) Orphanet J Rare Dis 1 21 16756677 10.1186/1750-1172-1-21
40. J Bertherat A Horvath L Groussin, et al. 2009 Mutations in regulatory subunit type 1A of cyclic adenosine 5′-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes J Clin Endocrinol Metab 94 2085 2091 19293268 10.1210/jc.2008-2333 1:CAS:528:DC%2BD1MXntFGmt7g%3D
41. SA Boikos CA Stratakis 2007 Carney complex: the first 20 years Curr Opin Oncol 19 24 29 17133108 10.1097/CCO.0b013e32801195eb 1:CAS:528: DC%2BD28Xht1Cnt7%2FP (Pubitemid 44885596)
42. LS Kirschner JA Carney SD Pack, et al. 2000 Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex Nat Genet 26 89 92 10973256 10.1038/79238 1:CAS:528:DC%2BD3cXmsVKrsr4%3D
43. PS Amieux GS McKnight 2002 The essential role of RI alpha in the maintenance of regulated PKA activity Ann N Y Acad Sci 968 75 95 12119269 10.1111/j.1749-6632.2002.tb04328.x 1:CAS:528:DC%2BD38XlvVSqs7c%3D (Pubitemid 34721873)
44. LS Kirschner F Sandrini J Monbo JP Lin JA Carney CA Stratakis 2000 Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex Hum Mol Genet 9 3037 3046 11115848 10.1093/hmg/9.20.3037 1:CAS:528:DC%2BD3MXjt1Wq (Pubitemid 32000777)
45. L Groussin LS Kirschner C Vincent-Dejean, et al. 2002 Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene in patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD Am J Hum Genet 71 1433 1442 12424709 10.1086/344579 1:CAS:528:DC%2BD3sXjsFSr (Pubitemid 36018745)
46. A Rothenbuhler CA Stratakis 2010 Clinical and molecular genetics of Carney complex Best Pract Res Clin Endocrinol Metab 24 389 399 20833331 10.1016/j.beem.2010.03.003 1:CAS:528:DC%2BC3cXhtFCls7rO
47. M Casey CJ Vaughan J He, et al. 2000 Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex J Clin Invest 106 R31 R38 10974026 10.1172/JCI10841 1:CAS:528:DC%2BD3cXmsVajtb8%3D
48. A Robinson-White TR Hundley M Shiferaw J Bertherat F Sandrini CA Stratakis 2003 Protein kinase-A activity in PRKAR1A-mutant cells, and regulation of mitogen-activated protein kinases ERK1/2 Hum Mol Genet 12 1475 1484 12812976 10.1093/hmg/ddg160 1:CAS:528:DC%2BD3sXkvVSmsbo%3D (Pubitemid 36857296)
49. A Zembowicz SM Knoepp T Bei, et al. 2007 Loss of expression of protein kinase a regulatory subunit 1alpha in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions Am J Surg Pathol 31 1764 1775 18059235 10.1097/PAS.0b013e318057faa7 (Pubitemid 350287576)
50. MW Ryan S Cunningham SY Xiao 2008 Maxillary sinus melanoma as the presenting feature of Carney complex Int J Pediatr Otorhinolaryngol 72 405 408 18082273 10.1016/j.ijporl.2007.10.022
51. G Mantovani S Bondioni AG Lania, et al. 2008 High expression of PKA regulatory subunit 1A protein is related to proliferation of human melanoma cells Oncogene 27 1834 1843 17906691 10.1038/sj.onc.1210831 1:CAS:528: DC%2BD1cXjsFChurw%3D (Pubitemid 351430825)
52. AK Lampe PJ Hampton K Woodford-Richens I Tomlinson CM Lawrence FS Douglas 2003 Laugier-Hunziker syndrome: an important differential diagnosis for Peutz-Jeghers syndrome J Med Genet 40 e77 12807976 10.1136/jmg.40.6.e77 1:STN:280:DC%2BD3s3otFKrtQ%3D%3D
53. S Rangwala CB Doherty R Katta 2010 Laugier-Hunziker syndrome: a case report and review of the literature Dermatol Online J 16 9 21199635
54. S Veraldi S Cavicchini C Benelli G Gasparini 1991 Laugier-Hunziker syndrome: a clinical, histopathologic, and ultrastructural study of four cases and review of the literature J Am Acad Dermatol 25 632 636 1791220 10.1016/0190-9622(91)70244-V 1:STN:280:DyaK387ms1ShtA%3D%3D
55. JH Ko YC Shih CS Chiu YH Chuang 2011 Dermoscopic features in Laugier-Hunziker syndrome J Dermatol 38 87 90 21175762 10.1111/j.1346-8138.2010. 01077.x
56. JF O'Neill WD James 1989 Inherited patterned lentiginosis in blacks Arch Dermatol 125 1231 1235 2673048 10.1001/archderm.125.9.1231 (Pubitemid 19229053)
57. Q Xing X Chen M Wang, et al. 2005 A locus for familial generalized lentiginosis without systemic involvement maps to chromosome 4q21.1-q22.3 Hum Genet 117 154 159 15841387 10.1007/s00439-005-1284-1 1:CAS:528: DC%2BD2MXltlCis7o%3D (Pubitemid 43136791)
58. I Dociu O Galaction-Nitelea N Sirjita V Murgu 1976 Centrofacial lentiginosis. A survey of 40 cases Br J Dermatol 94 39 43 766813 10.1111/j.1365-2133.1976.tb04339.x 1:STN:280:DyaE287js1Wquw%3D%3D
59. MR Nelen GW Padberg EA Peeters, et al. 1996 Localization of the gene for Cowden disease to chromosome 10q22-23 Nat Genet 13 114 116 8673088 10.1038/ng0596-114 1:CAS:528:DyaK28XksVWgurc%3D (Pubitemid 126528240)
60. MR Nelen WC van Staveren EA Peeters, et al. 1997 Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease Hum Mol Genet 6 1383 1387 9259288 10.1093/hmg/6.8.1383 1:CAS:528:DyaK2sXltVWjurc%3D (Pubitemid 27351082)
61. J Li C Yen D Liaw, et al. 1997 PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer Science 275 1943 1947 9072974 10.1126/science.275.5308.1943 1:CAS:528:DyaK2sXit1Wgtbk%3D (Pubitemid 27148818)
62. DM Li H Sun 1997 TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta Cancer Res 57 2124 2129 9187108 1:CAS:528:DyaK2sXjslGisrs%3D (Pubitemid 27247025)
63. PA Steck MA Pershouse SA Jasser, et al. 1997 Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers Nat Genet 15 356 362 9090379 10.1038/ng0497-356 1:CAS:528:DyaK2sXitF2hs70%3D (Pubitemid 27147102)
64. D Liaw DJ Marsh J Li, et al. 1997 Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome Nat Genet 16 64 67 9140396 10.1038/ng0597-64 1:CAS:528:DyaK2sXivFKhsb8%3D (Pubitemid 27198157)
65. DJ Marsh V Coulon KL Lunetta, et al. 1998 Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation Hum Mol Genet 7 507 515 9467011 10.1093/hmg/7.3.507 1:CAS:528:DyaK1cXitFWku74%3D (Pubitemid 28120643)
66. RJ Gorlin MM Cohen Jr. LM Condon BA Burke 1992 Bannayan-Riley-Ruvalcaba syndrome Am J Med Genet 44 307 314 1336932 10.1002/ajmg.1320440309 1:STN:280:DyaK3s7kt1OqsQ%3D%3D
67. KA Waite C Eng 2002 Protean PTEN: form and function Am J Hum Genet 70 829 844 11875759 10.1086/340026 1:CAS:528:DC%2BD38XivFClur8%3D (Pubitemid 34259300)
68. MH Tan J Mester C Peterson, et al. 2011 A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands Am J Hum Genet 88 42 56 21194675 10.1016/j.ajhg.2010.11.013 1:CAS:528:DC%2BC3MXktValsw%3D%3D
69. DJ Marsh JB Kum KL Lunetta, et al. 1999 PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome Hum Mol Genet 8 1461 1472 10400993 10.1093/hmg/8.8.1461 1:CAS:528:DyaK1MXltFagtLg%3D (Pubitemid 29374079)
70. C Eng 2003 PTEN: one gene, many syndromes Hum Mutat 22 183 198 12938083 10.1002/humu.10257 1:CAS:528:DC%2BD3sXos12msLo%3D (Pubitemid 37071635)
71. CA Stratakis LS Kirschner SE Taymans, et al. 1998 Carney complex, Peutz-Jeghers syndrome, Cowden disease, and Bannayan-Zonana syndrome share cutaneous and endocrine manifestations, but not genetic loci J Clin Endocrinol Metab 83 2972 2976 9709978 10.1210/jc.83.8.2972 1:CAS:528:DyaK1cXltlaht7k%3D (Pubitemid 28493808)
72. V Nose 2008 Familial non-medullary thyroid carcinoma: an update Endocr Pathol 19 226 240 18931957 10.1007/s12022-008-9045-z
73. GM Blumenthal PA Dennis 2008 PTEN hamartoma tumor syndromes Eur J Hum Genet 16 1289 1300 18781191 10.1038/ejhg.2008.162 1:CAS:528:DC%2BD1cXht1OntL%2FM
74. M Ming YY He 2009 PTEN: new insights into its regulation and function in skin cancer J Invest Dermatol 129 2109 2112 19340009 10.1038/jid.2009.79 1:CAS:528:DC%2BD1MXhtF2qsL3J
75. C Camisa JB Bikowski SG McDonald 1984 Cowden's disease. Association with squamous cell carcinoma of the tongue and perianal basal cell carcinoma Arch Dermatol 120 677 678 6721530 10.1001/archderm.120.5.677 1:STN:280: DyaL2c3gtFyqug%3D%3D (Pubitemid 14140289)
76. DD Nuss JL Aeling DE Clemons WN Weber 1978 Multiple hamartoma syndrome (Cowden's disease) Arch Dermatol 114 743 746 646396 10.1001/archderm.114.5.743 1:STN:280:DyaE1c7msVOktg%3D%3D (Pubitemid 8331234)
77. JA Hobert C Eng 2009 PTEN hamartoma tumor syndrome: an overview Genet Med 11 687 694 19668082 10.1097/GIM.0b013e3181ac9aea 1:CAS:528:DC%2BD1MXht1KjurfP
78. C Eng 2000 Will the real Cowden syndrome please stand up: revised diagnostic criteria J Med Genet 37 828 830 11073535 10.1136/jmg.37.11.828 1:STN:280:DC%2BD3M%2FktFemsg%3D%3D
79. I Sansal WR Sellers 2004 The biology and clinical relevance of the PTEN tumor suppressor pathway J Clin Oncol 22 2954 2963 15254063 10.1200/JCO.2004.02. 141 1:CAS:528:DC%2BD2cXpsVWktbk%3D (Pubitemid 41079915)
80. LC Cantley BG Neel 1999 New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway Proc Natl Acad Sci USA 96 4240 4245 10200246 10.1073/pnas.96.8.4240 1:CAS:528:DyaK1MXjs1ymtbg%3D (Pubitemid 29190320)
81. T Maehama JE Dixon 1998 The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate J Biol Chem 273 13375 13378 9593664 10.1074/jbc.273.22.13375 1:CAS:528:DyaK1cXjvVejsLk%3D (Pubitemid 28268370)
82. BD Manning LC Cantley 2003 United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling Biochem Soc Trans 31 573 578 12773158 10.1042/BST0310573 1:CAS:528:DC%2BD3sXktF2it7k%3D (Pubitemid 36750733)
83. DC Fingar J Blenis 2004 Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression Oncogene 23 3151 3171 15094765 10.1038/sj.onc.1207542 1:CAS:528:DC%2BD2cXjtFOmsb8%3D (Pubitemid 38638827)
84. H Tsao MC Mihm Jr. C Sheehan 2003 PTEN expression in normal skin, acquired melanocytic nevi, and cutaneous melanoma J Am Acad Dermatol 49 865 872 14576666 10.1016/S0190-9622(03)02473-3 (Pubitemid 37314875)
85. RJ Gorlin RC Anderson M Blaw 1969 Multiple lentigenes syndrome Am J Dis Child 117 652 662 5771505 1:STN:280:DyaF1M7ptVGnsQ%3D%3D
86. E Legius C Schrander-Stumpel E Schollen C Pulles-Heintzberger M Gewillig JP Fryns 2002 PTPN11 mutations in LEOPARD syndrome J Med Genet 39 571 574 12161596 10.1136/jmg.39.8.571 1:CAS:528:DC%2BD38XntFSktbY%3D (Pubitemid 34864560)
87. WS Chong W Klanwarin YC Giam 2004 Generalized lentiginosis in two children lacking systemic associations: case report and review of the literature Pediatr Dermatol 21 139 145 15078355 10.1111/j.0736-8046.2004.21211.x (Pubitemid 38507142)
88. Abdelmalek NF, Gerber TL, Menter A (2002) Cardiocutaneous syndromes and associations. J Am Acad Dermatol 46:161-183; quiz 83-86 (Pubitemid 34118371)
89. M Seishima Y Mizutani Y Shibuya C Arakawa R Yoshida T Ogata 2007 Malignant melanoma in a woman with LEOPARD syndrome: identification of a germline PTPN11 mutation and a somatic BRAF mutation Br J Dermatol 157 1297 1299 17927788 10.1111/j.1365-2133.2007.08229.x 1:CAS:528:DC%2BD1cXlsFeisQ%3D%3D (Pubitemid 350115702)
90. MC Digilio E Conti A Sarkozy, et al. 2002 Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene Am J Hum Genet 71 389 394 12058348 10.1086/341528 1:CAS:528:DC%2BD38XlvV2qtbo%3D (Pubitemid 34800254)
91. M Zenker 2009 Genetic and pathogenetic aspects of Noonan syndrome and related disorders Horm Res 72 Suppl 2 57 63 20029240 10.1159/000243782 1:CAS:528:DC%2BD1MXhsF2gtrrM
92. MA Razzaque T Nishizawa Y Komoike, et al. 2007 Germline gain-of-function mutations in RAF1 cause Noonan syndrome Nat Genet 39 1013 1017 17603482 10.1038/ng2078 1:CAS:528:DC%2BD2sXot1CmsLk%3D (Pubitemid 47185179)
93. B Pandit A Sarkozy LA Pennacchio, et al. 2007 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy Nat Genet 39 1007 1012 17603483 10.1038/ng2073 1:CAS:528:DC%2BD2sXot1CmsLs%3D (Pubitemid 47185177)
94. R Zoncu A Efeyan DM Sabatini 2011 mTOR: from growth signal integration to cancer, diabetes and ageing Nat Rev Mol Cell Biol 12 21 35 21157483 10.1038/nrm3025 1:CAS:528:DC%2BC3cXhsFGqsbnK
95. M Karbowniczek CS Spittle T Morrison H Wu EP Henske 2008 mTOR is activated in the majority of malignant melanomas J Invest Dermatol 128 980 987 17914450 10.1038/sj.jid.5701074 1:CAS:528:DC%2BD1cXjtFOmsL8%3D (Pubitemid 351374287)
96. RJ Shaw N Bardeesy BD Manning, et al. 2004 The LKB1 tumor suppressor negatively regulates mTOR signaling Cancer Cell 6 91 99 15261145 10.1016/j.ccr.2004.06.007 1:CAS:528:DC%2BD2cXmtlKntL4%3D (Pubitemid 38903165)
97. KG Lasithiotakis TW Sinnberg B Schittek, et al. 2008 Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells J Invest Dermatol 128 2013 2023 18323781 10.1038/jid.2008.44 1:CAS:528:DC%2BD1cXosVOmsLg%3D (Pubitemid 352001225)