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A mutational signature in gastric cancer suggests therapeutic strategies

Author

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  • Ludmil B. Alexandrov

    (Cancer Genome Project, Wellcome Trust Sanger Institute
    Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory
    Center for Nonlinear Studies, Los Alamos National Laboratory)

  • Serena Nik-Zainal

    (Cancer Genome Project, Wellcome Trust Sanger Institute
    Addenbrooke’s Hospital National Health Service (NHS) Trust)

  • Hoi Cheong Siu

    (The University of Hong Kong, Queen Mary Hospital)

  • Suet Yi Leung

    (The University of Hong Kong, Queen Mary Hospital)

  • Michael R Stratton

    (Cancer Genome Project, Wellcome Trust Sanger Institute)

Abstract

Targeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers. Recently, a mutational signature was associated with failure of double-strand DNA break repair by homologous recombination based on its high mutational burden in samples harbouring BRCA1 or BRCA2 mutations. In pancreatic cancer, all responders to platinum therapy exhibit this mutational signature including a sample that lacked any defects in BRCA1 or BRCA2. Here, we examine 10,250 cancer genomes across 36 types of cancer and demonstrate that, in addition to breast, ovarian and pancreatic cancers, gastric cancer is another cancer type that exhibits this mutational signature. Our results suggest that 7–12% of gastric cancers have defective double-strand DNA break repair by homologous recombination and may benefit from either platinum therapy or PARP inhibitors.

Suggested Citation

  • Ludmil B. Alexandrov & Serena Nik-Zainal & Hoi Cheong Siu & Suet Yi Leung & Michael R Stratton, 2015. "A mutational signature in gastric cancer suggests therapeutic strategies," Nature Communications, Nature, vol. 6(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9683
    DOI: 10.1038/ncomms9683
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    Cited by:

    1. Jurica Levatić & Marina Salvadores & Francisco Fuster-Tormo & Fran Supek, 2022. "Mutational signatures are markers of drug sensitivity of cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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