2026-05-17T05:52:34Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/175122024-11-29T22:42:08Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Santos, María
author
Lanillos, Javier
author
Roldan-Romero, Juan María
author
Caleiras, Eduardo
author
Montero-Conde, Cristina
author
Cascón, Alberto
author
Climent, Miguel Angel
author
Anguera, Georgia
author
Hernando, Susana
author
Laínez, Nuria
author
Robledo Batanero, Mercedes
author
Robles, Luis
author
de Velasco, Guillermo
author
García-Donas, Jesús
author
Rodriguez Antona, Cristina
funder
Ministerio de Ciencia e Innovación (España)
funder
European Union (EU)
2024-02-06T11:13:04Z
2024-02-06T11:13:04Z
2021-04
Genet Med . 2021;23(4):698-704
10.1038/s41436-020-01062-0
1530-0366
Genetics in medicine : official journal of the American College of Medical Genetics
33442023
http://hdl.handle.net/20.500.12105/17512
PURPOSE
Germline pathogenic variants are estimated to affect 3-5% of renal cell carcinoma (RCC) patients. However, higher mutational prevalence in non-clear cell RCC (non-ccRCC) and advanced disease has been suggested.
METHODS
To clarify the prevalence of pathogenic germline variants in metastatic RCC, we sequenced 29 cancer susceptibility genes in 294 unselected metastatic RCC cases plus 21 patients with clinical hereditary features. In 145 tumors, genes frequently mutated in RCC were sequenced and methylation was assessed in selected cases.
RESULTS
Germline variants in RCC predisposition genes (FH, VHL) were detected in 1.4% of the unselected metastatic patients, with higher frequency in non-ccRCC versus ccRCC (6.4% and 0.4%; P = 0.0025) and in younger patients (P = 0.036). Among the 315 studied patients, 14% of non-type 1 papillary cases (4 of 28), all metastatic <1 year after diagnosis, carried a FH germline variant with loss of heterozygosity and tumor genome hypermethylation. Variants in other cancer-associated genes (e.g., MUTYH, BRCA2, CHEK2) occurred in 5.1% of the unselected series, with unclear significance for RCC.
CONCLUSION
Our findings confirm a high prevalence of pathogenic germline variants in RCC predisposition genes in metastatic non-ccRCC, and highlight that metastatic patients with papillary type 2 or unconventional histologies compatible with FH would benefit from genetic screening.
eng
Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
journal article
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Prevalenceofpathogenicgermline_2021.pdf
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Prevalenceofpathogenicgermline_2021.pdf.txt