Characterization of genomic alterations in Chinese colorectal cancer patients.

ABSTRACT

OBJECTIVE: Colorectal cancer is one of the most prevalent types of cancer worldwide. Right-sided and left-sided colorectal cancer (RCC and LCC) patients respond differently to treatment. We aimed to identify the different mutational profile between RCC and LCC and provided evidence for future precision therapy. METHODS: A total of 630 Chinese colorectal cancer patients, including 467 (74.1%) LCC and 163 (25.9%) RCC, were enrolled in this cohort. Both formalin-fixed paraffin-embedded tumor tissues and matching blood samples were collected and deep sequenced targeting 450 cancer genes for genomic alteration analysis. Tumor mutational burden was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS: The most common mutated genes were TP53 (77.0%), APC (71.7%), KRAS (50.0%), SMAD4 (19.8%), PIK3CA (18.3%), FBXW7 (17.5%), TCF7L2 (12.5%), SOX9 (11.3%), LRP1B (10.8%), ARID1A (10.3%) and FAT4 (10.3%). The mutation frequencies of TP53 and APC in LCC were significantly higher than that of RCC, while the mutation frequency of PIK3CA was lower than that of RCC. Six gene fusions were specifically detected in RCC patients. Colorectal cancer sites were associated with gender (P = 4.15 × 10-5) and tumor differentiation (P = 0.059). In LCC, the gender-associated genes were FAT4, EP300, FAT1, LRP1, ARID1B, AR, FYN and TAF1, while in RCC, they were ARID1A, SMARCA4, LRP1 and GRIN2A. The mutations of 18 genes were associated with tumor differentiation (8 for LCC and 10 for RCC). High tumor mutational burden was more common in RCC. Our results implied more potential targeted drug therapy opportunities for RCC. CONCLUSION: We describe the different molecular characteristics of LCC and RCC. Our result supported a better prognosis of RCC than LCC in Chinese colorectal cancer patients.