Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer

AbstractOne of the most common mechanisms of immune evasion in MSI colorectal cancers (CRCs) is loss of HLA class I expression due to mutations inB2M gene which can become a negative predictor for checkpoint blockade therapy. The aim of this study was the determination of prevalence ofB2M somatic mutations in MSI CRC patients and relationship betweenB2M mutations and lymphocytes infiltration and other clinicopathological features as well as detection of methylation changes inB2M promoter region which can be another mechanism of immune escape. In our study, 37 MSI-H and 5 MSI-L patients were selected for screening ofB2M mutational and methylation status. The characterization of patients was based on standard histopathological diagnosis and TNM classification;BRAF,KRAS mutations, tumor-infiltrating lymphocytes and peritumoral lymphoid reaction were also determined. MSI analysis was performed using fragment analysis.B2M mutations were identified by Sanger sequencing, and methylation of CpG islands in promoter region was detected by methylation-specific PCR. Heterozygous mutations in theB2M gene were detected in five MSI-H patients (13.5%), while the mutation c.45_48delTTCT was determined in four patients and mutation c.276delC was found in two patients. One of these five patients was compound heterozygote harboring both mutations. Methylation of the promoter region of theB2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic change...
Source: Clinical and Experimental Medicine - Category: Research Source Type: research