Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes Journal Article


Authors: Riaz, N.; Blecua, P.; Lim, R. S.; Shen, R.; Higginson, D. S.; Weinhold, N.; Norton, L.; Weigelt, B.; Powell, S. N.; Reis-Filho, J. S.
Article Title: Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes
Abstract: BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair and are germ-line cancer pre-disposition genes that result in a syndrome of hereditary breast and ovarian cancer (HBOC). Whether germ-line or somatic alterations in these genes or other members of the HR pathway and if mono-or bi-allelic alterations of HR-related genes have a phenotypic impact on other cancers remains to be fully elucidated. Here, we perform a pan-cancer analysis of The Cancer Genome Atlas (TCGA) data set and observe that bi-allelic pathogenic alterations in homologous recombination (HR) DNA repair-related genes are prevalent across many malignancies. These bi-allelic alterations often associate with genomic features of HR deficiency. Further, in ovarian, breast and prostate cancers, bi-allelic alterations are mutually exclusive of each other. The combination of these two properties facilitates reclassification of variants of unknown significance affecting DNA repair genes, and may help personalize HR directed therapies in the clinic. © 2017 The Author(s).
Journal Title: Nature Communications
Volume: 8
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2017-10-11
Start Page: 857
Language: English
DOI: 10.1038/s41467-017-00921-w
PROVIDER: scopus
PMCID: PMC5636842
PUBMED: 29021619
DOI/URL:
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
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MSK Authors
  1. Simon Nicholas Powell
    165 Powell
  2. Larry Norton
    558 Norton
  3. Ronglai Shen
    127 Shen
  4. Nadeem Riaz
    210 Riaz
  5. Britta Weigelt
    260 Weigelt
  6. Jorge Sergio Reis
    283 Reis
  7. Raymond Sear Lim
    54 Lim