Hereditary leiomyomatosis and renal cell cancer: Update on clinical and molecular characteristics

Familial Cancer

Volumn 10, Issue 2, 2011, Pages 397-411

  Lehtonen, Heli J ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Fumarate hydratase (FH); HIF1; HLRCC; Kidney; Leiomyoma; Leiomyosarcoma; MCUL; Renal cell cancer; Tricarboxylic acid cycle

Indexed keywords

3 [2 [4 (4,4' DIFLUOROBENZHYDRYLIDENE)PIPERIDINO]ETHYL] 2,3 DIHYDRO 2 THIOXO 4(1H) QUINAZOLINONE; ANESTHETIC AGENT; BEVACIZUMAB; BORTEZOMIB; CHOLINERGIC RECEPTOR BLOCKING AGENT; CISPLATIN; CP 8947; ERLOTINIB; FUMARATE HYDRATASE; GLUCOSE; GLYCERYL TRINITRATE; HYPOXIA INDUCIBLE FACTOR 1; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PROGESTERONE RECEPTOR MODULATOR; SORAFENIB; SUNITINIB; UNCLASSIFIED DRUG;

ARTICLE; AUTOSOMAL DOMINANT INHERITANCE; CANCER SUSCEPTIBILITY; CARBON DIOXIDE LASER; CARCINOGENESIS; FAMILIAL CANCER; GENE INACTIVATION; GENETIC COUNSELING; GENETIC PREDISPOSITION; GLUCOSE TRANSPORT; GLYCOLYSIS; HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CANCER; HUMAN; KIDNEY CARCINOMA; LEIOMYOMA; LEIOMYOMATOSIS; LEIOMYOSARCOMA; NONHUMAN; PRIORITY JOURNAL; SKIN TUMOR; TUMOR GROWTH; TUMOR VASCULARIZATION; UTERUS TUMOR;

FEMALE; FUMARATE HYDRATASE; GENETIC COUNSELING; HETEROZYGOTE; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; KIDNEY NEOPLASMS; LEIOMYOMATOSIS; SKIN NEOPLASMS; UTERINE NEOPLASMS;

EID: 79958108040     PISSN: 13899600     EISSN: 15737292     Source Type: Journal    
DOI: 10.1007/s10689-011-9428-z     Document Type: Article

References (110)

1. WB Reed R Walker R Horowitz 1973 Cutaneous leiomyomata with uterine leiomyomata Acta Derm Venereol 53 409 416 4127477 1:STN:280: DyaE2c%2FivFartQ%3D%3D
2. V Launonen O Vierimaa M Kiuru, et al. 2001 Inherited susceptibility to uterine leiomyomas and renal cell cancer Proc Natl Acad Sci USA 98 3387 3392 11248088 1:CAS:528:DC%2BD3MXit1altL8%3D (Pubitemid 32220855)
3. NA Alam S Bevan M Churchman, et al. 2001 Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43 Am J Hum Genet 68 1264 1269 11283798 1:CAS:528:DC%2BD3MXkvF2nu7w%3D (Pubitemid 32424424)
4. IP Tomlinson NA Alam AJ Rowan, et al. 2002 Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer Nat Genet 30 406 410 11865300 1:CAS:528: DC%2BD38Xisl2lsLY%3D
5. NA Alam E Barclay AJ Rowan, et al. 2005 Clinical features of multiple cutaneous and uterine leiomyomatosis: an underdiagnosed tumor syndrome Arch Dermatol 141 199 206 15724016 (Pubitemid 40216262)
6. L Stewart GM Glenn P Stratton, et al. 2008 Association of germline mutations in the fumarate hydratase gene and uterine fibroids in women with hereditary leiomyomatosis and renal cell cancer Arch Dermatol 144 1584 1592 19075141
7. AB Zinn DS Kerr CL Hoppel 1986 Fumarase deficiency: a new cause of mitochondrial encephalomyopathy N Engl J Med 315 469 475 3736629 1:STN:280:DyaL283osVyrtw%3D%3D (Pubitemid 16034147)
8. M Deschauer Z Gizatullina A Schulze, et al. 2006 Molecular and biochemical investigations in fumarase deficiency Mol Genet Metab 88 146 152 16510303 1:CAS:528:DC%2BD28Xks1WrtrY%3D
9. R Petrova-Benedict BH Robinson TE Stacey, et al. 1987 Deficient fumarase activity in an infant with fumaricacidemia and its distribution between the different forms of the enzyme seen on isoelectric focusing Am J Hum Genet 40 257 266 3578275 1:STN:280:DyaL2s3htVWgtg%3D%3D (Pubitemid 17079446)
10. JP Bayley V Launonen IP Tomlinson 2008 The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency BMC Med Genet 9 20 18366737
11. Smit DL, Mensenkamp AR, Badeloe S et al. (2010) Hereditary leiomyomatosis and renal cell cancer in families referred for fumarate hydratase germline mutation analysis. Clin Genet
12. T Ahvenainen HJ Lehtonen R Lehtonen, et al. 2008 Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer Cancer Genet Cytogenet 183 83 88 18503824 1:CAS:528:DC%2BD1cXmsVeiu7Y%3D (Pubitemid 351715396)
13. S Ritzmann S Hanneken NJ Neumann, et al. 2006 Type 2 segmental manifestation of cutaneous leiomyomatosis in four unrelated women with additional uterine leiomyomas (Reed's syndrome) Dermatology 212 84 87 16319483 (Pubitemid 41779756)
14. JR Toro ML Nickerson MH Wei, et al. 2003 Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America Am J Hum Genet 73 95 106 12772087 1:CAS:528: DC%2BD3sXlsVOitLg%3D (Pubitemid 36793783)
15. MH Wei O Toure GM Glenn, et al. 2006 Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer J Med Genet 43 18 27 15937070 1:CAS:528:DC%2BD28XhtF2hsrs%3D (Pubitemid 43099991)
16. S Badeloe AJ van Geest AM van Marion, et al. 2008 Absence of fumarate hydratase mutation in a family with cutaneous leiomyosarcoma and renal cancer Int J Dermatol 47 Suppl 1 18 20 18986479
17. SF Cramer A Patel 1990 The frequency of uterine leiomyomas Am J Clin Pathol 94 435 438 2220671 1:STN:280:DyaK3M%2Fit1Gnsw%3D%3D (Pubitemid 20316570)
18. GP Flake J Andersen D Dixon 2003 Etiology and pathogenesis of uterine leiomyomas: a review Environ Health Perspect 111 1037 1054 12826476 1:CAS:528:DC%2BD3sXlvF2ksrw%3D (Pubitemid 36826884)
19. EA Pritts WH Parker DL Olive 2009 Fibroids and infertility: an updated systematic review of the evidence Fertil Steril 91 1215 1223 18339376
20. E D'Angelo J Prat 2010 Uterine sarcomas: a review Gynecol Oncol 116 131 139 19853898
21. Tavassoli FA, Devilee P (eds) (2003) World Health Organization classification of tumours: pathology & genetics of tumours of the breast and female genital organs. IARC Press, Lyon
22. M Kiuru V Launonen M Hietala, et al. 2001 Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology Am J Pathol 159 825 829 11549574 1:CAS:528:DC%2BD3MXnt12msL4%3D (Pubitemid 32847173)
23. HJ Lehtonen M Kiuru SK Ylisaukko-Oja, et al. 2006 Increased risk of cancer in patients with fumarate hydratase germline mutation J Med Genet 43 523 526 16155190 1:CAS:528:DC%2BD28XmvVKksbo%3D (Pubitemid 43927328)
24. Lehtonen HJ (2008) Molecular and clinical characteristics of tricarboxylic acid cycle-associated tumors. Dissertation, University of Helsinki
25. SK Ylisaukko-oja M Kiuru HJ Lehtonen, et al. 2006 Analysis of fumarate hydratase mutations in a population-based series of early onset uterine leiomyosarcoma patients Int J Cancer 119 283 287 16477632 1:CAS:528: DC%2BD28XmsVOjt7g%3D
26. HJ Lehtonen I Blanco JM Piulats, et al. 2007 Conventional renal cancer in a patient with fumarate hydratase mutation Hum Pathol 38 793 796 17270241 1:CAS:528:DC%2BD2sXkt1ajtbg%3D (Pubitemid 46560795)
27. NC Wortham NA Alam E Barclay, et al. 2006 Aberrant expression of apoptosis proteins and ultrastructural aberrations in uterine leiomyomas from patients with hereditary leiomyomatosis and renal cell carcinoma Fertil Steril 86 961 971 16962107 1:CAS:528:DC%2BD28Xht1eht7zK (Pubitemid 44485023)
28. HT Cohen FJ McGovern 2005 Renal-cell carcinoma N Engl J Med 353 2477 2490 16339096 1:CAS:528:DC%2BD2MXhtlShurnM (Pubitemid 41770167)
29. Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds) (2004) World Health Organization classification of tumours: pathology & genetics of tumours of the urinary system and male genital organs. IARC Press, Lyon
30. Koski TA (2010) Molecular genetic background of tumours in hereditary leiomyomatosis and renal cell cancer syndrome. Dissertation, University of Helsinki
31. I Alrashdi S Levine J Paterson, et al. 2010 Hereditary leiomyomatosis and renal cell carcinoma: very early diagnosis of renal cancer in a paediatric patient Fam Cancer 9 239 243 19967458
32. M Kiuru V Launonen 2004 Hereditary leiomyomatosis and renal cell cancer (HLRCC) Curr Mol Med 4 869 875 15579034 1:CAS:528:DC%2BD2cXhtVGlsb3M (Pubitemid 39585732)
33. NA Alam AJ Rowan NC Wortham, et al. 2003 Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency Hum Mol Genet 12 1241 1252 12761039 1:CAS:528:DC%2BD3sXkt1Wru7Y%3D (Pubitemid 36722604)
34. I Chan T Wong A Martinez-Mir, et al. 2005 Familial multiple cutaneous and uterine leiomyomas associated with papillary renal cell cancer Clin Exp Dermatol 30 75 78 15663510 1:STN:280:DC%2BD2M%2Fjs12ksw%3D%3D (Pubitemid 40188325)
35. GS Chuang A Martinez-Mir DE Engler, et al. 2006 Multiple cutaneous and uterine leiomyomata resulting from missense mutations in the fumarate hydratase gene Clin Exp Dermatol 31 118 121 16309500 1:STN:280:DC%2BD2MnivFWkuw%3D%3D
36. GS Chuang A Martinez-Mir A Geyer, et al. 2005 Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata J Am Acad Dermatol 52 410 416 15761418
37. MA Refae N Wong F Patenaude, et al. 2007 Hereditary leiomyomatosis and renal cell cancer: an unusual and aggressive form of hereditary renal carcinoma Nat Clin Pract Oncol 4 256 261 17392716 1:CAS:528:DC%2BD2sXjs12rsb8%3D (Pubitemid 46510535)
38. S Badeloe M van Geel MA van Steensel, et al. 2006 Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature Exp Dermatol 15 735 741 16881969 1:CAS:528:DC%2BD28XhtVGit7vL (Pubitemid 44145243)
39. MK Frey MJ Worley Jr KP Heyman, et al. 2010 A case report of hereditary leiomyomatosis and renal cell cancer Am J Obstet Gynecol 202 e8 e9 20510956
40. RL Grubb 3rd ME Franks J Toro, et al. 2007 Hereditary leiomyomatosis and renal cell cancer: a syndrome associated with an aggressive form of inherited renal cancer J Urol 177 2074 2079 17509289 1:CAS:528:DC%2BD2sXmslKlurc%3D discussion 2079-80
41. MJ Merino C Torres-Cabala P Pinto, et al. 2007 The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome Am J Surg Pathol 31 1578 1585 17895761 (Pubitemid 47482473)
42. B Delahunt JN Eble 1997 Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors Mod Pathol 10 537 544 9195569 1:STN:280:DyaK2szjvFSjuw%3D%3D (Pubitemid 27293491)
43. S Badeloe KY van Spaendonck-Zwarts MA van Steensel, et al. 2009 Wilms tumour as a possible early manifestation of hereditary leiomyomatosis and renal cell cancer? Br J Dermatol 160 707 709 19183174 1:CAS:528:DC%2BD1MXktFCntLg%3D
44. TA Koski HJ Lehtonen KJ Jee, et al. 2009 Array comparative genomic hybridization identifies a distinct DNA copy number profile in renal cell cancer associated with hereditary leiomyomatosis and renal cell cancer Genes Chromosomes Cancer 48 544 551 19373782 1:CAS:528:DC%2BD1MXmvVWrtLk%3D
45. N Terada K Ichioka Y Matsuta, et al. 2002 The natural history of simple renal cysts J Urol 167 21 23 11743266 (Pubitemid 34024487)
46. ZI Carrim JT Murchison 2003 The prevalence of simple renal and hepatic cysts detected by spiral computed tomography Clin Radiol 58 626 629 12887956 1:STN:280:DC%2BD3szlsFegsg%3D%3D (Pubitemid 37121138)
47. PJ Pollard B Spencer-Dene D Shukla, et al. 2007 Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway Cancer Cell 11 311 319 17418408 1:CAS:528:DC%2BD2sXksFWjsr8%3D (Pubitemid 46518311)
48. SJ Mandriota KJ Turner DR Davies, et al. 2002 HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron Cancer Cell 1 459 468 12124175 1:CAS:528: DC%2BD38XltVKjsbw%3D (Pubitemid 41039126)
49. SK Ylisaukko-oja C Cybulski R Lehtonen, et al. 2006 Germline fumarate hydratase mutations in patients with ovarian mucinous cystadenoma Eur J Hum Genet 14 880 883 16639410 1:CAS:528:DC%2BD28XmtVSmtrs%3D (Pubitemid 43923375)
50. M Lamba S Verma R Prokopetz, et al. 2005 Multiple cutaneous and uterine leiomyomas associated with gastric GIST J Cutan Med Surg 9 332 335 16699905 (Pubitemid 44491083)
51. E Campione A Terrinoni A Orlandi, et al. 2007 Cerebral cavernomas in a family with multiple cutaneous and uterine leiomyomas associated with a new mutation in the fumarate hydratase gene J Invest Dermatol 127 2271 2273 17476294 1:CAS:528:DC%2BD2sXptVWhtrk%3D (Pubitemid 47258493)
52. A Varol K Stapleton T Roscioli 2006 The syndrome of hereditary leiomyomatosis and renal cell cancer (HLRCC): the clinical features of an individual with a fumarate hydratase gene mutation Australas J Dermatol 47 274 276 17034471 (Pubitemid 44536224)
53. L Matyakhina RJ Freedman I Bourdeau, et al. 2005 Hereditary leiomyomatosis associated with bilateral, massive, macronodular adrenocortical disease and atypical Cushing syndrome: a clinical and molecular genetic investigation J Clin Endocrinol Metab 90 3773 3779 15741255 1:CAS:528: DC%2BD2MXkvFCksrw%3D (Pubitemid 41014354)
54. LG Carvajal-Carmona NA Alam PJ Pollard, et al. 2006 Adult leydig cell tumors of the testis caused by germline fumarate hydratase mutations J Clin Endocrinol Metab 91 3071 3075 16757530 1:CAS:528:DC%2BD28XosFGhsbY%3D (Pubitemid 44271757)
55. KD McKelvey Jr S Siraj J Kelsay, et al. 2010 Male infertility associated with hereditary leiomyomatosis and renal cell carcinoma Fertil Steril 93 2075.e1 2075.e2
56. M Kiuru R Lehtonen J Arola, et al. 2002 Few FH mutations in sporadic counterparts of tumor types observed in hereditary leiomyomatosis and renal cell cancer families Cancer Res 62 4554 4557 12183404 1:CAS:528:DC%2BD38XmsVShsro%3D
57. M Kiuru R Lehtonen H Eerola, et al. 2005 No germline FH mutations in familial breast cancer patients Eur J Hum Genet 13 506 509 15523491 1:CAS:528:DC%2BD2MXisFKitLY%3D (Pubitemid 40520944)
58. S Bevan SM Edwards A Ardern Jones, et al. 2003 Germline mutations in fumarate hydratase (FH) do not predispose to prostate cancer Prostate Cancer Prostatic Dis 6 12 14 12664059 1:CAS:528:DC%2BD3sXitl2jsr4%3D (Pubitemid 36432615)
59. R Lehtonen M Kiuru S Vanharanta, et al. 2004 Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors Am J Pathol 164 17 22 14695314 1:CAS:528:DC%2BD2cXlsVChtg%3D%3D (Pubitemid 38364585)
60. R Lehtonen M Kiuru A Rokman, et al. 2003 No fumarate hydratase (FH) mutations in hereditary prostate cancer J Med Genet 40 e19 12624148 1:STN:280:DC%2BD3s7hs1Gltg%3D%3D
61. KT Barker S Bevan R Wang, et al. 2002 Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas Br J Cancer 87 446 448 12177782 1:CAS:528: DC%2BD38XmtVOnurk%3D (Pubitemid 34983569)
62. KL Gross CI Panhuysen MS Kleinman, et al. 2004 Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: genetic linkage analysis and FISH studies Genes Chromosomes Cancer 41 183 190 15334541 1:CAS:528: DC%2BD2cXptVemsr4%3D (Pubitemid 39299288)
63. M Maradin K Fumic H Hansikova, et al. 2006 Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations J Inherit Metab Dis 29 683 16972175 1:STN:280:DC%2BD28rks1aitQ%3D%3D
64. Shih VE, Mandell R (2009) Fumarate hydratase deficiency. Available via http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fum
65. BT Kinsella S Doonan 1986 Nucleotide sequence of a cDNA coding for mitochondrial fumarase from human liver Biosci Rep 6 921 929 3828494 1:CAS:528:DyaL2sXktVWktbc%3D (Pubitemid 17030657)
66. E Tolley I Craig 1975 Presence of two forms of fumarase (Fumarate Hydratase E.C. 4.2.1.2) in mammalian cells: immunological characterization and genetic analysis in somatic cell hybrids. Confirmation of the assignment of a gene necessary for the enzyme expression to human chromosome 1 Biochem Genet 13 867 883 812482 1:CAS:528:DyaE28XlslSjtw%3D%3D
67. E Sass S Karniely O Pines 2003 Folding of fumarase during mitochondrial import determines its dual targeting in yeast J Biol Chem 278 45109 45116 12960177 1:CAS:528:DC%2BD3sXoslyqtbs%3D (Pubitemid 37432643)
68. A Lorenzato M Olivero M Perro, et al. 2008 A cancer-predisposing "hot spot" mutation of the fumarase gene creates a dominant negative protein Int J Cancer 122 947 951 17960613 1:CAS:528:DC%2BD1cXhsFShsb0%3D
69. F Rongioletti V Fausti B Ferrando, et al. 2010 A novel missense mutation in fumarate hydratase in an italian patient with a diffuse variant of cutaneous leiomyomatosis (Reed's syndrome) Dermatology 221 378 380 21051878 1:STN:280:DC%2BC3M%2FlvFSmug%3D%3D
70. P Vahteristo TA Koski L Naatsaari, et al. 2010 No evidence for a genetic modifier for renal cell cancer risk in HLRCC syndrome Fam Cancer 9 245 251 20091131
71. E Gottlieb IP Tomlinson 2005 Mitochondrial tumour suppressors: a genetic and biochemical update Nat Rev Cancer 5 857 866 16327764 1:CAS:528: DC%2BD2MXht1WitLfE (Pubitemid 41746030)
72. HX Hao O Khalimonchuk M Schraders, et al. 2009 SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma Science 325 1139 1142 19628817 1:CAS:528:DC%2BD1MXhtVersr%2FF
73. GL Semenza 2010 Oxygen homeostasis Wiley Interdiscip Rev Syst Biol Med 2 336 361 20836033 1:CAS:528:DC%2BC3cXmtVSrtr4%3D
74. L O'Flaherty J Adam LC Heather, et al. 2010 Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism Hum Mol Genet 19 3844 3851 20660115
75. MA Selak SM Armour ED MacKenzie, et al. 2005 Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase Cancer Cell 7 77 85 15652751 1:CAS:528:DC%2BD2MXhsVait74%3D (Pubitemid 40126384)
76. PJ Pollard JJ Briere NA Alam, et al. 2005 Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations Hum Mol Genet 14 2231 2239 15987702 1:CAS:528:DC%2BD2MXmt1ert78%3D (Pubitemid 41418022)
77. JS Isaacs YJ Jung DR Mole, et al. 2005 HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability Cancer Cell 8 143 153 16098467 1:CAS:528: DC%2BD2MXps1Ojt7k%3D (Pubitemid 41132743)
78. ED MacKenzie MA Selak DA Tennant, et al. 2007 Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells Mol Cell Biol 27 3282 3289 17325041 1:CAS:528:DC%2BD2sXltFCks7k%3D (Pubitemid 46685207)
79. Y Pan KD Mansfield CC Bertozzi, et al. 2007 Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro Mol Cell Biol 27 912 925 17101781 1:CAS:528:DC%2BD2sXhtFGhtLo%3D (Pubitemid 46174556)
80. P Koivunen M Hirsila AM Remes, et al. 2007 Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF J Biol Chem 282 4524 4532 17182618 1:CAS:528:DC%2BD2sXhsFKgsrY%3D (Pubitemid 47100953)
81. WH Catherino CM Mayers T Mantzouris, et al. 2007 Compensatory alterations in energy homeostasis characterized in uterine tumors from hereditary leiomyomatosis and renal cell cancer Fertil Steril 88 1039 1048 17383644 1:CAS:528:DC%2BD2sXhtlShsLjO (Pubitemid 47513039)
82. S Vanharanta PJ Pollard HJ Lehtonen, et al. 2006 Distinct expression profile in fumarate-hydratase-deficient uterine fibroids Hum Mol Genet 15 97 103 16319128 1:CAS:528:DC%2BD2MXhtlChsrvP (Pubitemid 43020108)
83. P Pollard N Wortham E Barclay, et al. 2005 Evidence of increased microvessel density and activation of the hypoxia pathway in tumours from the hereditary leiomyomatosis and renal cell cancer syndrome J Pathol 205 41 49 15586379 (Pubitemid 40029091)
84. H Ashrafian L O'Flaherty J Adam, et al. 2010 Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis Cancer Res 70 9153 9165 20978192 1:CAS:528:DC%2BC3cXhsVWmsLrF
85. N Raimundo J Ahtinen K Fumic, et al. 2008 Differential metabolic consequences of fumarate hydratase and respiratory chain defects Biochim Biophys Acta 1782 287 294 18313410 1:CAS:528:DC%2BD1cXlsFyjtb4%3D
86. AE Greijer E van der Wall 2004 The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis J Clin Pathol 57 1009 1014 15452150 1:CAS:528:DC%2BD2cXps1Kls78%3D (Pubitemid 39331346)
87. B Costa D Dettori A Lorenzato, et al. 2010 Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis FASEB J 24 2680 2688 20354140 1:CAS:528:DC%2BC3cXhtVeisbbK
88. JP Bayley P Devilee 2010 Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree? Curr Opin Genet Dev 20 324 329 20304625 1:CAS:528:DC%2BC3cXntlCru7k%3D
89. S Sudarshan C Sourbier HS Kong, et al. 2009 Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species Mol Cell Biol 29 4080 4090 19470762 1:CAS:528: DC%2BD1MXptFehsb0%3D
90. O Warburg F Wind E Negelein 1927 The metabolism of tumors in the body J Gen Physiol 8 519 530 19872213 1:CAS:528:DyaB2sXitlyhuw%3D%3D
91. RJ Gillies RA Gatenby 2007 Adaptive landscapes and emergent phenotypes: why do cancers have high glycolysis? J Bioenerg Biomembr 39 251 257 17624581 1:CAS:528:DC%2BD2sXhtF2iu7zI (Pubitemid 47619378)
92. T Bui CB Thompson 2006 Cancer's sweet tooth Cancer Cell 9 419 420 16766260 1:CAS:528:DC%2BD28Xmt1eksLs%3D (Pubitemid 43832194)
93. H Yan DW Parsons G Jin, et al. 2009 IDH1 and IDH2 mutations in gliomas N Engl J Med 360 765 773 19228619 1:CAS:528:DC%2BD1MXitFWru7o%3D
94. O Yogev O Yogev E Singer, et al. 2010 Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response PLoS Biol 8 e1000328 20231875
95. Pithukpakorn M, Toro JR (2007) Hereditary leiomyomatosis and renal cell cancer. Available via http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book= gene&part=hlrcc
96. WH Parker 2007 Uterine myomas: management Fertil Steril 88 255 271 17658523 (Pubitemid 47212168)
97. WH Catherino M Malik P Driggers, et al. 2010 Novel, orally active selective progesterone receptor modulator CP8947 Inhibits leiomyoma cell proliferation without adversely affecting endometrium or myometrium J Steroid Biochem Mol Biol 122 279 286 20493256 1:CAS:528:DC%2BC3cXht1Gjt7vL
98. WM Linehan PA Pinto G Bratslavsky, et al. 2009 Hereditary kidney cancer: unique opportunity for disease-based therapy Cancer 115 2252 2261 19402075 1:CAS:528:DC%2BD1MXmtVOksbo%3D
99. CP Pavlovich LS Schmidt 2004 Searching for the hereditary causes of renal-cell carcinoma Nat Rev Cancer 4 381 393 15122209 1:CAS:528: DC%2BD2cXjsFSksr4%3D (Pubitemid 38579484)
100. GN Gupta J Peterson KN Thakore, et al. 2010 Oncological outcomes of partial nephrectomy for multifocal renal cell carcinoma greater than 4 Cm J Urol 184 59 63 20478582
101. EA Singer G Bratslavsky WM Linehan, et al. 2010 Targeted therapies for non-clear renal cell carcinoma Target Oncol 5 119 129 20680492
102. Vladimir AV, Youfeng Y, Beatriz AW et al (2010) 367 evaluation of the VEGF-VEGF receptor axis in hereditary leiomyomatosis renal cell carcinoma (HLRCC) kidney tumors. J Urol 183
103. RE Airley A Mobasheri 2007 Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics Chemotherapy 53 233 256 17595539 1:CAS:528: DC%2BD2sXnsl2gtbY%3D (Pubitemid 47074647)
104. Y Yang VA Valera HM Padilla-Nash, et al. 2010 UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer Cancer Genet Cytogenet 196 45 55 19963135 1:CAS:528:DC%2BD1MXhsFahs7rL
105. H Xie VA Valera MJ Merino, et al. 2009 LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer Mol Cancer Ther 8 626 635 19276158 1:CAS:528:DC%2BD1MXjtVyjtrs%3D
106. DA Tennant C Frezza ED MacKenzie, et al. 2009 Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death Oncogene 28 4009 4021 19718054 1:CAS:528:DC%2BD1MXhtVKhs7rO
107. E Temes S Martin-Puig B Acosta-Iborra, et al. 2005 Activation of HIF-prolyl hydroxylases by R59949, an inhibitor of the diacylglycerol kinase J Biol Chem 280 24238 24244 15849364 1:CAS:528:DC%2BD2MXltlKgs7s%3D (Pubitemid 40884913)
108. P Gao H Zhang R Dinavahi, et al. 2007 HIF-dependent antitumorigenic effect of antioxidants in vivo Cancer Cell 12 230 238 17785204 1:CAS:528:DC%2BD2sXhtVKqsb3E (Pubitemid 47333417)
109. C Sourbier V Valera-Romero A Giubellino, et al. 2010 Increasing reactive oxygen species as a therapeutic approach to treat hereditary leiomyomatosis and renal cell carcinoma Cell Cycle 9 4183 4189 20953139 1:CAS:528: DC%2BC3MXit1ahurY%3D
110. PJ Pollard PJ Ratcliffe 2009 Cancer. Puzzling patterns of predisposition Science 324 192 194 19359573 1:CAS:528:DC%2BD1MXkvFyhsrY%3D