A mutational signature in gastric cancer suggests therapeutic strategies.
Siu, Hoi Cheong
Leung, Suet Yi
Stratton, Michael R
Springer Science and Business Media LLC
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Alexandrov, L. B., Nik-Zainal, S., Siu, H. C., Leung, S. Y., & Stratton, M. R. (2015). A mutational signature in gastric cancer suggests therapeutic strategies.. Nat Commun, 6 8683. https://doi.org/10.1038/ncomms9683
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.
Humans, Neoplasms, Breast Neoplasms, Stomach Neoplasms, Pancreatic Neoplasms, BRCA1 Protein, BRCA2 Protein, DNA Repair, Mutation, Female, Male, DNA Breaks
External DOI: https://doi.org/10.1038/ncomms9683
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284499
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/