New genetic variations discovered in KRAS wild-type cetuximab resistant chinese colorectal cancer patients

Molecular Carcinogenesis
Changwen JingJifeng Feng

Abstract

To perform a comprehensive genomic analysis of colorectal cancer (CRC) tumor to detect genetic variants and identify novel resistant mutations associated with cetuximab-resistance in CRC patients. A retrospective study was performed using whole exome sequencing (WES) to identify common genetic factors from 22 cetuximab-sensitive and 10 cetuximab-resistant patients. In all 10 cetuximab-resistant patients, we discovered there are 37 significantly mutated genes (SMGs). CYP4A11 was the most frequently mutated gene in cetuximab-resistant patients. BCAS1 and GOLGA6L1 were found to be among the second group of frequently mutated genes with a frequency of 60%. After cosine similarity analysis, three mutational signatures (signature a, b, and c) were found in all CRC tumors, similar to signature 1, 5, and 6 in COSMIC, respectively. Gene ontology analysis was performed on SMGs and found 12 enriched GO terms. Four genes are enriched in six specific Kyoto Encyclopedia of Genes and Genomes pathway groups, including the metabolism of xenobiotics by cytochrome P450, steroid hormone biosynthesis, retinol metabolism, and drug metabolism. Our data supports a network composed of SMGs and cellular signaling pathways that have been positively linke...Continue Reading

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