Comprehensive analysis of mutational features of colorectal cancer and multiple primary cancers including colorectal component: Data from the Cancer Genome Atlas

Abstract

Colorectal cancer (CRC) is the second in mortality among cancers with high incidence worldwide. About 5 % of patients had a previous oncopathology and 20 % develop a second malignancy. CRC molecular genetic mechanisms in primary multiple cancers (MPCs) are not fully understood. This study aimed to investigate mutational characteristics of primary CRC compared to MPCs with colorectal component. 336 CRC patients and 52 MPCs patients with a colorectal component (C97CRC) (TCGA-COAD data) were included. Comparative bioinformatics analysis of genetic mutations, their interactions, effect on signaling pathways, survival rate, and druggable categories was conducted. CRC was characterized by PIK3CA and APC mutations, while 17 mutations in other genes were identified in C97CRC. In CRC group, co-occurring somatic variants in TP53/APC and KRAS/APC were the most common, while in C97CRC, KRAS/SOX9 was specifically found. TP53/SYNE1, TP53/MUC16, and TP53/TTN mutational combinations were associated with a decreased survival rate in CRC group. Collagen type VI α3-chain protease and its inhibitor were suggested as specific druggable targets in C97CRC group. The differences in mutational profiles between groups may indicate evolutionary features of CRC as a primary and secondary malignancy. Described druggable categories open up prospects for treatment development of CRC and MPCs with a colorectal component.