A mutational signature in gastric cancer suggests therapeutic strategies

doi:10.1038/ncomms9683

Title: A mutational signature in gastric cancer suggests therapeutic strategies

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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. Furthermore, 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.

Authors:

; Nik-Zainal, Serena ^[2] ; Siu, Hoi Cheong ^[3] ; Leung, Suet Yi ^[3] ; Stratton, Michael R. ^[4]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wellcome Trust Sanger Institute, Hinxton (United Kingdom)
Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Addenbrooke's Hospital National Health Service (NHS) Trust, Cambridge (United Kingdom)
The Univ. of Hong Kong, Queen Mary Hospital, Pokfulam (Hong Kong)
Wellcome Trust Sanger Institute, Hinxton (United Kingdom)

Publication Date:: 2015-10-29

Report Number(s):: LA-UR-15-24068
Journal ID: ISSN 2041-1723; ncomms9683

Grant/Contract Number:: AC52-06NA25396

Type:: Accepted Manuscript

Journal Name:: Nature Communications

Additional Journal Information:: Journal Volume: 6; Journal ID: ISSN 2041-1723

Publisher:: Nature Publishing Group

Research Org:: Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Org:: USDOE

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; biological sciences; cancer; genetics; medical research

OSTI Identifier:: 1236756


                    Alexandrov, Ludmil B., Nik-Zainal, Serena, Siu, Hoi Cheong, Leung, Suet Yi, and Stratton, Michael R.. A mutational signature in gastric cancer suggests therapeutic strategies.  United States: N. p.,  
        Web.  doi:10.1038/ncomms9683.

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                    Alexandrov, Ludmil B., Nik-Zainal, Serena, Siu, Hoi Cheong, Leung, Suet Yi, & Stratton, Michael R.. A mutational signature in gastric cancer suggests therapeutic strategies.  United States.  doi:10.1038/ncomms9683.

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                    Alexandrov, Ludmil B., Nik-Zainal, Serena, Siu, Hoi Cheong, Leung, Suet Yi, and Stratton, Michael R.. 2015.  
        "A mutational signature in gastric cancer suggests therapeutic strategies".  United States.  
        doi:10.1038/ncomms9683.  https://www.osti.gov/servlets/purl/1236756.

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@article{osti_1236756,

  title        = {A mutational signature in gastric cancer suggests therapeutic strategies},

  author       = {Alexandrov, Ludmil B. and Nik-Zainal, Serena and Siu, Hoi Cheong and Leung, Suet Yi and Stratton, Michael R.},

  abstractNote = {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. Furthermore, 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.},

  doi          = {10.1038/ncomms9683},

  journal      = {Nature Communications},

  number       = ,

  volume       = 6,

  place        = {United States},

  year         = {2015},

  month        = {10}

}

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10.1038/ncomms9683
https://doi.org/10.1038/ncomms9683

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Title: A mutational signature in gastric cancer suggests therapeutic strategies

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