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

## TL;DR

This study identifies new mutated genes in colorectal cancer and finds that mutation burden and TP53 mutations affect patient survival.

## Contribution

The study identifies new driver genes and establishes survival associations with mutation burden and TP53 mutations in colorectal cancer.

## Key findings

- PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 are significantly mutated genes in CRC.
- Hypermutated tumors show improved survival with increased mutation burden (HR = 0.42).
- TP53 mutations with predicted 0% transcriptional activity are linked to poorer CRC-specific survival (HR = 1.53).

## 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.