期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-17386-z
关键词
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资金
- NIH/NCI Cancer Center Support Grant [P30 CA015704]
- National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, U01 CA164930, R01 CA176272]
- National Cancer Institute (NCI), National Institutes of Health (NIH) [U01 CA167551]
- Ontario Familial Colorectal Cancer Registry [NCI/NIH U01/U24 CA074783]
- Seattle Colorectal Cancer Family Registry [NCI/NIH U01/U24 CA074794]
- National Institutes of Health [R01 CA076366, U01 CA074783]
- American Cancer Society
- German Research Council [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1, BR 1704/17-1]
- Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany
- German Federal Ministry of Education and Research [01KH0404, 01ER0814, 01ER0815, 01ER1505A, 01ER1505B]
- Ontario Research Fund
- Canadian Institutes of Health Research
- Ontario Institute for Cancer Research through Ontario Ministry of Research and Innovation
- Centers for Disease Control and Prevention National Program of Cancer Registries
- National Cancer Institute Surveillance Epidemiology and End Results program
- Ontario Ministry of Research and Innovation, Ontario, Canada
Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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