Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this...

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Detalhes bibliográficos
Autores: Elkholi, Islam E., Iorio, Massimo Di, Fahiminiya, Somayyeh, Arcand, Suzanna L., Han, Hyerim, Nogué, Clara, Behl, Supriya, Hamel, Nancy, Giroux, Sylvie, Ladurantaye, Manon de, Aleynikova, Olga, Gotlieb, Walter H., Côté, Jean-François, Rousseau, François, Tonin, Patricia N., Provencher, Diane, Mesmasson, Anne-Marie, Akbari, Mohammad R., Rivera, Barbara, Foulkes, William D.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/175108
Acesso em linha:https://hdl.handle.net/2445/175108
Access Level:acceso abierto
Palavra-chave:Càncer de mama
Càncer d'ovari
Càncer d'endometri
Breast cancer
Ovarian cancer
Endometrial cancer
Descrição
Resumo:The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case-control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations.

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