Prevalence of Homologous Recombination Deficiency Among Patients With Germline RAD51C/D Breast or Ovarian Cancer

IMPORTANCE RAD51C and RAD51D are involved in DNA repair by homologous recombination. Germline pathogenic variants (PVs) in these genes are associated with an increased risk of ovarian and breast cancer. Understanding the homologous recombination deficiency (HRD) status of tumors from patients with g...

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Detalles Bibliográficos
Autores: Torres Esquius, Sara|||0000-0001-7540-7284, Llop Guevara, Alba|||0000-0002-7913-9472, Gutiérrez-Enríquez, Sara|||0000-0002-1711-6101, Romey, Marcel, Teule, Alex|||0000-0003-0028-7200, Llort, Gemma|||0000-0001-9987-7862, Herrero, Ana, Sánchez-Henarejos, Pilar, Vallmajó, Anna, González-Santiago, Santiago|||0000-0002-4787-0236, Chirivella, Isabel|||0000-0002-0733-3276, Cano, Juana María|||0000-0002-2493-0988, Graña, Begoña|||0000-0003-2008-8188, Simonetti, Sara|||0000-0003-2406-030X, Díaz de Corcuera, Isabel, Ramon y Cajal, Teresa|||0000-0003-3490-3585, Sanz, Judit, Serrano, Sara, Otero, Andrea, Churruca, Cristina, Sánchez-Heras, Ana Beatriz|||0000-0003-1742-5374, Servitja, Sonia|||0000-0001-6988-4519, Guillén-Ponce, Carmen, Brunet, Joan|||0000-0003-1945-3512, Denkert, Carsten, Serra, Violeta|||0000-0001-6620-1065, Balmaña Gelpí, Judith|||0000-0002-0762-6415
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:306344
Acceso en línea:https://ddd.uab.cat/record/306344
https://dx.doi.org/urn:doi:10.1001/jamanetworkopen.2024.7811
Access Level:acceso abierto
Palabra clave:Adult
Aged
Breast Neoplasms
DNA-Binding Proteins
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Homologous Recombination
Humans
Middle Aged
Ovarian Neoplasms
Prevalence
Retrospective Studies
Spain
Descripción
Sumario:IMPORTANCE RAD51C and RAD51D are involved in DNA repair by homologous recombination. Germline pathogenic variants (PVs) in these genes are associated with an increased risk of ovarian and breast cancer. Understanding the homologous recombination deficiency (HRD) status of tumors from patients with germline PVs in RAD51C/D could guide therapeutic decision-making and improve survival. OBJECTIVE To characterize the clinical and tumor characteristics of germline RAD51C/D PV carriers, including the evaluation of HRD status. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 91 index patients plus 90 relatives carrying germline RAD51C/D PV (n = 181) in Spanish hospitals from January 1, 2014, to December 31, 2021. Genomic and functional HRD biomarkers were assessed in untreated breast and ovarian tumor samples (n = 45) from June 2022 to February 2023. MAIN OUTCOMES AND MEASURES Clinical and pathologic characteristics were assessed using descriptive statistics. Genomic HRD by genomic instability scores, functional HRD by RAD51, and gene-specific loss of heterozygosity were analyzed. Associations between HRD status and tumor subtype, age at diagnosis, and gene-specific loss of heterozygosity in RAD51C/D were investigated using logistic regression or the t test. RESULTS A total of 9507 index patients were reviewed, and 91 patients (1.0%) were found to carry a PV in RAD51C/D; 90 family members with a germline PV in RAD51C/D were also included. A total of 157 of carriers (86.7%) were women and 181 (55.8%) had received a diagnosis of cancer, mainly breast cancer or ovarian cancer. The most prevalent PVs were c.1026+5_1026+7del (11 of 56 [19.6%]) and c.709C.

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