Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer
| Autor: | Somayyeh Fahiminiya, Olga Aleynikova, Anne-Marie Mes-Masson, Diane Provencher, Barbara Rivera, HyeRim Han, Nancy Hamel, Supriya Behl, Suzanna L. Arcand, Sylvie Giroux, Massimo Di Iorio, Jean-François Côté, François Rousseau, Manon de Ladurantaye, Clara Nogué, Walter H. Gotlieb, Islam E. Elkholi, Patricia N. Tonin, Mohammad R. Akbari, William D. Foulkes |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Oncology medicine.medical_specialty Somatic cell Science DNA Mutational Analysis Population Càncer d'ovari Breast Neoplasms Article Germline Càncer de mama Breast cancer Endometrial cancer Ovarian cancer Molecular genetics Internal medicine Exome Sequencing medicine Humans Genetic Predisposition to Disease Clinical genetics education Gene Alleles Germ-Line Mutation Ovarian Neoplasms Gynaecological cancer MRE11 Homologue Protein education.field_of_study Multidisciplinary business.industry Quebec medicine.disease Pedigree MRE11A Càncer d'endometri Mutation Medicine Hereditary Breast and Ovarian Cancer Syndrome Female business |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-021-81106-w |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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