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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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
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spelling Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.Santos, MaríaLanillos, JavierRoldan-Romero, Juan MaríaCaleiras, EduardoMontero-Conde, CristinaCascón, AlbertoCliment, Miguel AngelAnguera, GeorgiaHernando, SusanaLaínez, NuriaRobledo Batanero, MercedesRobles, Luisde Velasco, GuillermoGarcía-Donas, JesúsRodriguez Antona, CristinaCarcinoma, Renal CellKidney NeoplasmsGerm CellsGerm-Line MutationHumansMutationPrevalencePURPOSE 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.ElsevierMinisterio de Ciencia e Innovación (España)European Union (EU)20242024-02-0620212021-04-0120212021-04-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/17512reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/175122026-06-12T12:43:37Z
dc.title.none.fl_str_mv Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
title Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
spellingShingle Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
Santos, María
Carcinoma, Renal Cell
Kidney Neoplasms
Germ Cells
Germ-Line Mutation
Humans
Mutation
Prevalence
title_short Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
title_full Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
title_fullStr Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
title_full_unstemmed Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
title_sort Prevalence of pathogenic germline variants in patients with metastatic renal cell carcinoma.
dc.creator.none.fl_str_mv 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
author Santos, María
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
European Union (EU)
dc.subject.none.fl_str_mv Carcinoma, Renal Cell
Kidney Neoplasms
Germ Cells
Germ-Line Mutation
Humans
Mutation
Prevalence
topic Carcinoma, Renal Cell
Kidney Neoplasms
Germ Cells
Germ-Line Mutation
Humans
Mutation
Prevalence
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-04-01
2021
2021-04-01
2024
2024-02-06
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17512
url http://hdl.handle.net/20.500.12105/17512
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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