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A mutational signature in gastric cancer suggests therapeutic strategies.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Alexandrov, Ludmil B  ORCID logo  https://orcid.org/0000-0003-3596-4515
Nik-Zainal, Serena 
Siu, Hoi Cheong 
Leung, Suet Yi 
Stratton, Michael R 

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.

Description

Keywords

BRCA1 Protein, BRCA2 Protein, Breast Neoplasms, DNA Breaks, DNA Repair, Female, Humans, Male, Mutation, Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

6

Publisher

Springer Science and Business Media LLC