Molecular characteristics of 14 239 patients with microsatellite instability colorectal cancer

Objective To analyze their molecular characteristics of microsatellite instability (MSI) by sequencing colorectal cancer patients in Sichuan region. Methods Next generation sequencing (NGS) was used to test 14 239 colon cancer patients from 2017 to 2022 in the Third People's Hospital of Chengdu for single nucleotide variation (SNV), insertion-deletion (InDel), copy number variation (CNV), fusion, MSI, tumor mutational burden (TMB), and Epstein-Barr virus (EBV). The clinical and molecular characteristics of highly microsatellite unstable (MSI-H) patients (MSI-H group, n=1 018) and microsatellite stable (MSS) patients (MSS group, n=13 221) were compared. Results The incidence rate of MSI in colorectal cancer was 7.15%, and detection rate of MSI varied in terms of age at diagnosis, tumour location and sample type. TMB was significantly higher in patients with MSI-H than in patients with microsatellite stable (MSS) (92.8 mutations/Mb vs 12.7 mutations/Mb, P＜0.05). EBV positivity in patients with colorectal cancer was 0.43%, but no patient with positive EBV was found in MSI-H. ERBB2, PIK3CA and BRAF all had significantly higher mutation frequencies in the MSI-H group, however, the positive rates of APC (51.26% vs 70.76%, χ2=168.823, P<0.01), TP53 (27.76% vs 69.54%, χ2=739.882, P<0.01) and NRAS (1.86% vs 3.98%, χ2=11.445, P<0.01) were higher in the MSS group. Furthermore, MSI-H patients had a higher proportion of carrying a mismatch repair (MMR) gene variant (P＜0.05). Conclusion MSI-H and MSS types of colorectal cancer in Sichuan have different molecular characteristics and differ in TMB and EBV infections.