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1.	Zaidi, Syed H., et al. (author) Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival 2020 In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1 Journal article (peer-reviewed)abstract 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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Type of publication: journal article (1)

Type of content: peer-reviewed (1)

Author/Editor: Chang-Claude, Jenny (1); Berndt, Sonja I (1); Brenner, Hermann (1); Thibodeau, Stephen N (1); Lin, Yi (1); Qu, Conghui (1); show more...; Buchanan, Daniel D. (1); Chan, Andrew T. (1); Figueiredo, Jane C. (1); Gallinger, Steven (1); Gsur, Andrea (1); Harlid, Sophia, 1978 ... (1); Hidaka, Akihisa (1); Harrison, Tabitha A. (1); Hoffmeister, Michael (1); Huyghe, Jeroen R. (1); Jenkins, Mark A. (1); Moreno, Victor (1); Newcomb, Polly A. (1); Ogino, Shuji (1); van Guelpen, Bethany (1); Hsu, Li (1); Peters, Ulrike (1); Campbell, Peter T. (1); Hopper, John L. (1); Wheeler, David A (1); Alwers, Elizabeth (1); Drew, David A. (1); Huang, Wen-Yi (1); Sun, Wei (1); Fuchs, Charles S (1); Mardis, Elaine R (1); Cao, Yin (1); Brezina, Stefanie (1); Hudson, Thomas J. (1); Garraway, Levi A (1); Papadopoulos, Nickol ... (1); Banbury, Barbara L. (1); Connolly, Charles M. (1); McPherson, John D. (1); Borozan, Ivan (1); Zaidi, Syed H. (1); Phipps, Amanda I. (1); Trinh, Quang M. (1); Giannakis, Marios (1); Heisler, Lawrence E. (1); Luo, Xuemei (1); Nishihara, Reiko (1); Reid, Emma E.G. (1); Um, Caroline Y. (1); show less...

University: Umeå University (1)

Language: English (1)

Research subject (UKÄ/SCB): Medical and Health Sciences (1)

Year: 2020 (1)

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