气候变化领域集成服务门户(CCPortal): Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer

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DOI	10.1038/s41559-021-01470-8
	Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer
	Woolston A.; Barber L.J.; Griffiths B.; Pich O.; Lopez-Bigas N.; Matthews N.; Rao S.; Watkins D.; Chau I.; Starling N.; Cunningham D.; Gerlinger M.
发表日期	2021
ISSN	2397-334X
起始页码	1024
结束页码	1032
卷号	5 期号:7
英文摘要	Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. It is unknown which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis (a transient cetuximab-induced increase in mutation generation) contributes in patients. Here, we investigate these questions in exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated CRCs. Mutation loads did not increase from baseline to progression, and evidence for a contribution of adaptive mutagenesis was limited. However, the chemotherapy-induced mutational signature SBS17b was the main contributor of specific KRAS/NRAS and EGFR driver mutations that are enriched at acquired resistance. Detectable SBS17b activity before treatment predicted shorter progression-free survival and the evolution of these specific mutations during subsequent cetuximab treatment. This result suggests that chemotherapy mutagenesis can accelerate resistance evolution. Mutational signatures may be a new class of cancer evolution predictor. ? 2021, The Author(s), under exclusive licence to Springer Nature Limited.
语种	英语
scopus关键词	antineoplastic agent; cetuximab; colorectal tumor; genetics; human; mutation; Antineoplastic Agents; Cetuximab; Colorectal Neoplasms; Humans; Mutation
来源期刊	Nature Ecology & Evolution
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/256915
作者单位	Translational Oncogenomics Laboratory, The Institute of Cancer Research, London, United Kingdom; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avan?ats (ICREA), Barcelona, Spain; Tumour Profiling Unit, The Institute of Cancer Research, London, United Kingdom; Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, United Kingdom
推荐引用方式 GB/T 7714	Woolston A.,Barber L.J.,Griffiths B.,et al. Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer[J],2021,5(7).
APA	Woolston A..,Barber L.J..,Griffiths B..,Pich O..,Lopez-Bigas N..,...&Gerlinger M..(2021).Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer.Nature Ecology & Evolution,5(7).
MLA	Woolston A.,et al."Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer".Nature Ecology & Evolution 5.7(2021).