Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.

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 R...

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Detalles Bibliográficos
Autores: Santos, María, Lanillos, Javier, Roldan-Romero, Juan María, Caleiras, Eduardo, Montero-Conde, Cristina, Cascón, Alberto, Climent, Miguel Angel, Anguera, Georgia, Hernando, Susana, Laínez, Nuria, Robledo Batanero, Mercedes, Robles, Luis, de Velasco, Guillermo, García-Donas, Jesús, Rodriguez Antona, Cristina
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17512
Acceso en línea:http://hdl.handle.net/20.500.12105/17512
Access Level:acceso abierto
Palabra clave:Carcinoma, Renal Cell
Kidney Neoplasms
Germ Cells
Germ-Line Mutation
Humans
Mutation
Prevalence
Descripción
Sumario: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.

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