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

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اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
      Genetic Predisposition to Disease* ; Mutation*; Breast Neoplasms/*genetics ; MRE11 Homologue Protein/*genetics ; Ovarian Neoplasms/*genetics; Adult ; Alleles ; Breast Neoplasms/diagnosis ; DNA Mutational Analysis ; Female ; Germ-Line Mutation ; Hereditary Breast and Ovarian Cancer Syndrome/genetics ; Humans ; MRE11 Homologue Protein/metabolism ; Ovarian Neoplasms/diagnosis ; Pedigree ; Quebec ; Exome Sequencing
    • نبذة مختصرة :
      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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    • الرقم المعرف:
      0 (MRE11 protein, human)
      EC 3.1.- (MRE11 Homologue Protein)
    • الموضوع:
      Date Created: 20210129 Date Completed: 20210916 Latest Revision: 20221207
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC7844268
    • الرقم المعرف:
      10.1038/s41598-021-81106-w
    • الرقم المعرف:
      33510186