Climate Change Data Portal
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). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。