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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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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/175108
Acceso en línea:https://hdl.handle.net/2445/175108
Access Level:acceso abierto
Palabra clave:Càncer de mama
Càncer d'ovari
Càncer d'endometri
Breast cancer
Ovarian cancer
Endometrial cancer
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spelling Investigating the causal role of MRE11A p.E506* in breast and ovarian cancerElkholi, Islam E.Iorio, Massimo DiFahiminiya, SomayyehArcand, Suzanna L.Han, HyerimNogué, ClaraBehl, SupriyaHamel, NancyGiroux, SylvieLadurantaye, Manon deAleynikova, OlgaGotlieb, Walter H.Côté, Jean-FrançoisRousseau, FrançoisTonin, Patricia N.Provencher, DianeMesmasson, Anne-MarieAkbari, Mohammad R.Rivera, BarbaraFoulkes, William D.Càncer de mamaCàncer d'ovariCàncer d'endometriBreast cancerOvarian cancerEndometrial cancerThe 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.Springer Nature2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/175108Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-021-81106-wScientific Reports, 2021, vol. 11https://doi.org/10.1038/s41598-021-81106-wcc by (c) Elkholi et al., 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1751082026-05-27T06:46:51Z
dc.title.none.fl_str_mv Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer
title Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer
spellingShingle Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer
Elkholi, Islam E.
Càncer de mama
Càncer d'ovari
Càncer d'endometri
Breast cancer
Ovarian cancer
Endometrial 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
dc.creator.none.fl_str_mv 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.
author Elkholi, Islam E.
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de mama
Càncer d'ovari
Càncer d'endometri
Breast cancer
Ovarian cancer
Endometrial cancer
topic Càncer de mama
Càncer d'ovari
Càncer d'endometri
Breast cancer
Ovarian cancer
Endometrial cancer
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/175108
url https://hdl.handle.net/2445/175108
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-81106-w
Scientific Reports, 2021, vol. 11
https://doi.org/10.1038/s41598-021-81106-w
dc.rights.none.fl_str_mv cc by (c) Elkholi et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Elkholi et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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