Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer
Abstract 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 investig...
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2021
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oai:doaj.org-article:64c0a0aadac845d4b26d482428971ff52021-12-02T10:48:03ZInvestigating the causal role of MRE11A p.E506* in breast and ovarian cancer10.1038/s41598-021-81106-w2045-2322https://doaj.org/article/64c0a0aadac845d4b26d482428971ff52021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81106-whttps://doaj.org/toc/2045-2322Abstract 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.Islam E. ElkholiMassimo Di IorioSomayyeh FahiminiyaSuzanna L. ArcandHyeRim HanClara NoguéSupriya BehlNancy HamelSylvie GirouxManon de LadurantayeOlga AleynikovaWalter H. GotliebJean-François CôtéFrançois RousseauPatricia N. ToninDiane ProvencherAnne-Marie MesMassonMohammad R. AkbariBarbara RiveraWilliam D. FoulkesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
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Medicine R Science Q Islam E. Elkholi Massimo Di Iorio Somayyeh Fahiminiya Suzanna L. Arcand HyeRim Han Clara Nogué Supriya Behl Nancy Hamel Sylvie Giroux Manon de Ladurantaye Olga Aleynikova Walter H. Gotlieb Jean-François Côté François Rousseau Patricia N. Tonin Diane Provencher Anne-Marie MesMasson Mohammad R. Akbari Barbara Rivera William D. Foulkes Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer |
| description |
Abstract 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. |
| format |
article |
| author |
Islam E. Elkholi Massimo Di Iorio Somayyeh Fahiminiya Suzanna L. Arcand HyeRim Han Clara Nogué Supriya Behl Nancy Hamel Sylvie Giroux Manon de Ladurantaye Olga Aleynikova Walter H. Gotlieb Jean-François Côté François Rousseau Patricia N. Tonin Diane Provencher Anne-Marie MesMasson Mohammad R. Akbari Barbara Rivera William D. Foulkes |
| author_facet |
Islam E. Elkholi Massimo Di Iorio Somayyeh Fahiminiya Suzanna L. Arcand HyeRim Han Clara Nogué Supriya Behl Nancy Hamel Sylvie Giroux Manon de Ladurantaye Olga Aleynikova Walter H. Gotlieb Jean-François Côté François Rousseau Patricia N. Tonin Diane Provencher Anne-Marie MesMasson Mohammad R. Akbari Barbara Rivera William D. Foulkes |
| author_sort |
Islam E. Elkholi |
| title |
Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer |
| title_short |
Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer |
| title_full |
Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer |
| title_fullStr |
Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer |
| title_full_unstemmed |
Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer |
| title_sort |
investigating the causal role of mre11a p.e506* in breast and ovarian cancer |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/64c0a0aadac845d4b26d482428971ff5 |
| work_keys_str_mv |
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| _version_ |
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