Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival.

Nature Communications
Syed H ZaidiUlrike Peters

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.

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Citations

Oct 27, 2020·Computational and Structural Biotechnology Journal·Ekaterina ShevchenkoTatu Pantsar
May 1, 2021·Cancers·Magdalena C Liebl, Thomas G Hofmann
Jul 4, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Claire GalloisDavid Tougeron
Oct 12, 2021·Molecular and Clinical Oncology·Melchior De Giraud D'AgayFrancois Ghiringhelli

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Methods Mentioned

BETA
AmpliSeq
exome sequencing
ubiquitination
Assay
PCR

Clinical Trials Mentioned

NCT01876511

Software Mentioned

BWA
GECCO
VarDict
Burrows
Sequenom
ANNOVAR
- Aligner
- MEM
MutSigCV
Strelka

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