Mutations of the VHL gene in sporadic renal cell carcinoma: Definition of a risk factor for VHL patients to develop an RCC

Gallou, Catherine; Joly, Dominique; Méjean, A.; Staroz, F.; Martin, Natacha; Tarlet, Georges; Orfanelli, M.-T.; Bouvier, Raymonde; Droz, Dominique; Chrétien, Yves; Maréchal, J; Richard, Stéphane; Junien, Claudine; Béroud, Christophe

doi:10.1002/(sici)1098-1004(1999)13:6<464::aid-humu6>3.0.co;2-a

Cited by 129 publications

(64 citation statements)

References 29 publications

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“…Somatic biallelic inactivating VHL mutations are involved in sporadic clear cell RCC tumorigenesis in up to 80% of samples [Bailly et al, 1995;Foster et al, 1994;Gallou, 1999Gallou, , 2001Gallou, , 2004Gnarra et al, 1994;Kanno et al, 1996;Prowse et al, 1997;Shuin et al, 1994;Suzuki et al, 1997;van Houwelingen et al, 2005]. Similarly, sporadic RCC in patients exposed to the industrial solvent trichloroethylene (TCE) display similar histopathological features and also harbor VHL mutations [Brauch, 2004;Brüning et al, 1997;Charbotel et al, 2007;Shiao, 2009;Wells et al, 2009].…”

Section: Sporadic Diseasesmentioning

confidence: 99%

“…Germline mutations leading to a truncated pVHL confer a 40% risk higher of developing RCC when compared to patients with germline missense mutations [Gallou et al, 1999[Gallou et al, , 2004. Some have found that VHL deletions extending to include the actin-regulator gene HSPC300 appear to lower the risk of RCC and retinal angiomas development [Franke et al, 2009;Maranchie et al, 2004].…”

Section: Renal Cell Carcinoma Associated With Vhl Diseasementioning

confidence: 99%

“…Of these 993, 44% were frameshift, 8.5% were nonsense, and 38% were missense. Collectively, it seems that, like RCC associated with VHL disease, a truncated pVHL supports tumor growth in the kidney [Gallou et al, 1999]. Large studies have found no association between mutation types and TNM grade or nuclear grade [Gallou et al, 1999[Gallou et al, , 2001van Houwelingen et al, 2005].…”

Section: Sporadic Renal Cell Carcinomamentioning

confidence: 99%

“…Patients with mutations at codon 167, such as c. 499 C4T (p.Arg167Trp) and c.500G4A (p.Arg167Gln), have a 63% risk of developing pheochromocytomas [Crossey et al, 1994b;Gallou et al, 1999;Gross et al, 1996]. According to Zbar et al [1996] 7% of Japanese, French, and United Kingdom families and 11% of National Cancer Institute patients have mutations at codon 167.…”

Section: Pathogenic Variantsmentioning

confidence: 99%

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Genetic analysis of von Hippel-Lindau disease

et al. 2010

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Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype-phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information. Hum Mutat 31:521-537,

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Section: Sporadic Diseasesmentioning

confidence: 99%

Section: Renal Cell Carcinoma Associated With Vhl Diseasementioning

confidence: 99%

Section: Sporadic Renal Cell Carcinomamentioning

confidence: 99%

Section: Pathogenic Variantsmentioning

confidence: 99%

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Genetic analysis of von Hippel-Lindau disease

et al. 2010

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“…9 -12 Somatic inactivation of the VHL gene is found in up to 70% of sporadic clear-cell RCC whereas somatic c-MET mutations only occur in 13% of papillary tumours. [13][14][15][16] Prolonged exposure to trichloroethylene during metal machining is associated with clear-cell RCC harbouring a specific pattern of VHL somatic mutations; the identification of this putative mechanism increases the probability for a causative role of trichloroethylene in RCC. 12,17 We recently were made aware of an unexpected number of RCC occurring in a French factory that specialised in vitamin A, vitamin E and methionine synthesis.…”

mentioning

confidence: 99%

High incidence of renal tumours in vitamins A and E synthesis workers: A new cause of occupational cancer?

Richard

Carrette

Béroud

et al. 2004

Intl Journal of Cancer

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Dear Sir,Renal cell carcinoma (RCC) is the most common adult kidney tumour, accounting for around 3% of human malignancies. 1 Its incidence is about 11/100,000 person-years in industrial countries and is increasing as the result of both increases in the prevalence of risk factors and in use of diagnostic imaging procedures. 2-3 Main histological subtypes include clear-cell (75%), papillary (10%) and chromophobe (5%) RCC. Complete surgical resection is considered to be curative for localised RCC but 30% of patients have metastatic disease at diagnosis and RCC is responsible for about 95,000 deaths per year world-wide. 1 Little is known regarding etiological factors of RCC. 2,4 Familial RCC syndromes are estimated at less than 5%; the 2 main conditions are von Hippel-Lindau disease, related to the tumour-suppressor VHL gene, for clear-cell RCC; and hereditary papillary RCC, caused by the c-MET proto-oncogene. 5 Most cases of RCC are thought to be sporadic and many factors are known to increase the risk. Tobacco smoking, obesity (particularly among women), high blood pressure and/or medication prescribed to treat this condition are the main established, although modest, risk factors. 6 -8 A number of reports have also pointed out the potential nephrocarcinogenic effect of occupational exposure to trichloroethylene, gasoline, petroleum products, asbestos, cadmium and iron processing fumes; corresponding epidemiological studies, however, are sometimes controversial. 9 -12 Somatic inactivation of the VHL gene is found in up to 70% of sporadic clear-cell RCC whereas somatic c-MET mutations only occur in 13% of papillary tumours. [13][14][15][16] Prolonged exposure to trichloroethylene during metal machining is associated with clear-cell RCC harbouring a specific pattern of VHL somatic mutations; the identification of this putative mechanism increases the probability for a causative role of trichloroethylene in RCC. 12,17 We recently were made aware of an unexpected number of RCC occurring in a French factory that specialised in vitamin A, vitamin E and methionine synthesis. Between March 1994 and October 2002, 10 cases of RCC were detected in workers from this factory that currently employs 612 men and 116 women. Because of the use of vinyl chloride, a well-documented liver carcinogen, an annual abdominal ultrasonography was progressively introduced in worker medical surveillance in the end of the 1980s. The first RCC was detected by chance in 1994 in a 48-year-old man, who had worked at vitamin A synthesis from 1979 to 1988. To date, 9 further men with RCC have been discovered through systematic ultrasonography and confirmed by CT-scan [ Table I]. Mean age at diagnosis was 52.3 Ϯ 7.8 years and mean diameter of tumour was 2.9 Ϯ 1.0 cm. All patients were successfully operated upon (6 patients underwent a nephrectomy and 4 were treated by conservative surgery) and were free of disease in March 2003. Review of tumour slides identified 7 clear-cell and 3 papillary RCC. The renal tumour was unique in 9 patients and multifoc...

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UMD (Universal Mutation Database): A generic software to build and analyze locus-specific databases

et al. 2000

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The human genome is thought to contain about 80,000 genes and presently only 3,000 are known to be implicated in genetic diseases. In the near future, the entire sequence of the human genome will be available and the development of new methods for point mutation detection will lead to a huge increase in the identification of genes and their mutations associated with genetic diseases as well as cancers, which is growing in frequency in industrial states. The collection of these mutations will be critical for researchers and clinicians to establish genotype/phenotype correlations. Other fields such as molecular epidemiology will also be developed using these new data. Consequently, the future lies not in simple repositories of locus-specific mutations but in dynamic databases linked to various computerized tools for their analysis and that can be directly queried on-line. To meet this goal, we devised a generic software called UMD (Universal Mutation Database). It was developed as a generic software to create locus-specific databases (LSDBs) with the 4 th Dimension® package from ACI. This software includes an optimized structure to assist and secure data entry and to allow the input of various clinical data. Thanks to the flexible structure of the UMD software, it has been successfully adapted to nine genes either involved in cancer (APC, P53, RB1, MEN1, SUR1, VHL, and WT1) or in genetic diseases (FBN1 and LDLR). Four new LSDBs are under construction (VLCAD, MCAD, KIR6, and COL4A5). Finally, the data can be transferred to core databases. Hum Mutat 15:86-94, 2000.

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Mutations of the VHL gene in sporadic renal cell carcinoma: Definition of a risk factor for VHL patients to develop an RCC

Cited by 129 publications

References 29 publications

Genetic analysis of von Hippel-Lindau disease

Genetic analysis of von Hippel-Lindau disease

High incidence of renal tumours in vitamins A and E synthesis workers: A new cause of occupational cancer?

UMD (Universal Mutation Database): A generic software to build and analyze locus-specific databases

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