Abstract 5763: Comprehensive characteristics between genomic alterations and tumor differentiation in Chinese patients with colorectal cancer

Abstract

Abstract Background: Colorectal cancer (CRC) is a malignant tumor that seriously threatens human health. Valuable diagnostic and prognostic biomarkers are urgently needed for colorectal cancer. We aim to analyze the mutational characteristics of Chinese CRC patients with different tumor differentiation degree, in order to improve the diagnosis and prognosis of this population. Methods: We retrospectively analyzed tumor tissue specimens from colorectal cancer patients who were treated at the First Affiliated Hospital of Shanxi Medical University from 2019 to 2021. Targeted NGS for 450 genes was performed in OrigiMed (Shanghai, China), a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: There were 35 males (55.6%) and 28 females (44.4%) with a median age of 60 (range 23-87) years were involved, including 55 moderately and well differentiated and 8 poorly differentiated colorectal tumors. The mutational frequency of BRAF in the poorly differentiated group was significantly higher than that in moderately and well differentiated group(25% vs. 1.8%, p=0.04). The mutational frequencies of the chromosome folding pathway, notch pathway, and PI3K pathway in poorly differentiated group were significantly lower than that in moderately and well differentiated group(p=0.975X10-15,p=0.97 X 10-26,and p=0.00517, respectively). In this study, the mutations of PDCD1 (programmed cell death 1) and TSC2 Significantly associated with tumor mutation burden (p=0.007 and p=0.047, respectively). In addition, high-frequency co-mutations of chromosome folding-related genes and DNA damage repair-related genes, such as co-mutations between ARID1A-MLH1,KMT2D-MSH6,KMT2D-MSH2, KMT2D-BRCA1, ARID1A-CHEK2, were detected in this study. Conclusions: We compared the genomic alterations between well-differentiated group and poorly-differentiated group in Chinese CRC patients. Our data showed significant differences in mutational frequency of chromosome folding pathways, notch pathways, and PI3K pathways between well-differentiated group and poorly-differentiated group. Meanwhile, we also identified the high-frequency and complex co-mutation characteristics of chromosome folding pathway genes and DNA damage repair genes in Chinese CRC patients. Citation Format: Xiaolong Cui, Aigang Ren, Hao Chen, Yaoliang Huo, Yanwu Zeng, Hao Zhang, Meizhen Hu, He Huang, Yuntong Guo. Comprehensive characteristics between genomic alterations and tumor differentiation in Chinese patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5763.