| Literature DB >> 35121966 |
Erin Pleasance1, Emma Titmuss1, Laura Williamson1, Harwood Kwan1, Luka Culibrk1, Eric Y Zhao1, Katherine Dixon2, Kevin Fan1, Reanne Bowlby1, Martin R Jones1, Yaoqing Shen1, Jasleen K Grewal1, Jahanshah Ashkani1, Kathleen Wee1, Cameron J Grisdale1, My Linh Thibodeau1,2,3, Zoltan Bozoky1, Hillary Pearson4, Elisa Majounie1, Tariq Vira1, Reva Shenwai1, Karen L Mungall1, Eric Chuah1, Anna Davies1, Mya Warren1, Caralyn Reisle1, Melika Bonakdar1, Gregory A Taylor1, Veronika Csizmok1, Simon K Chan1, Zusheng Zong1, Steve Bilobram1, Amir Muhammadzadeh1, Darryl D'Souza1, Richard D Corbett1, Daniel MacMillan1, Marcus Carreira1, Caleb Choo1, Dustin Bleile1, Sara Sadeghi1, Wei Zhang1, Tina Wong1, Dean Cheng1, Scott D Brown1, Robert A Holt1, Richard A Moore1, Andrew J Mungall1, Yongjun Zhao1, Jessica Nelson1, Alexandra Fok1, Yussanne Ma1, Michael K C Lee5, Jean-Michel Lavoie5, Shehara Mendis5, Joanna M Karasinska6, Balvir Deol5, Ana Fisic5, David F Schaeffer6,7, Stephen Yip7, Kasmintan Schrader2,3, Dean A Regier8, Deirdre Weymann8, Stephen Chia5, Karen Gelmon5, Anna Tinker5, Sophie Sun5, Howard Lim5, Daniel J Renouf5,6, Janessa Laskin5, Steven J M Jones1,2,9, Marco A Marra10,11.
Abstract
Advanced and metastatic tumors with complex treatment histories drive cancer mortality. Here we describe the POG570 cohort, a comprehensive whole-genome, transcriptome and clinical dataset, amenable for exploration of the impacts of therapies on genomic landscapes. Previous exposure to DNA-damaging chemotherapies and mutations affecting DNA repair genes, including POLQ and genes encoding Polζ, were associated with genome-wide, therapy-induced mutagenesis. Exposure to platinum therapies coincided with signatures SBS31 and DSB5 and, when combined with DNA synthesis inhibitors, signature SBS17b. Alterations in ESR1, EGFR, CTNNB1, FGFR1, VEGFA and DPYD were consistent with drug resistance and sensitivity. Recurrent noncoding events were found in regulatory region hotspots of genes including TERT, PLEKHS1, AP2A1 and ADGRG6. Mutation burden and immune signatures corresponded with overall survival and response to immunotherapy. Our data offer a rich resource for investigation of advanced cancers and interpretation of whole-genome and transcriptome sequencing in the context of a cancer clinic.Entities:
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Year: 2020 PMID： 35121966 DOI： 10.1038/s43018-020-0050-6
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347