A mutational signature in gastric cancer suggests therapeutic strategies.
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Publication Date
2015-10-29Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
6
Pages
8683
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
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
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.
Keywords
BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, DNA Breaks, DNA Repair, Female, Humans, Male, Mutation, Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms
Identifiers
External DOI: https://doi.org/10.1038/ncomms9683
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284499
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