Somatic mutations of the coding microsatellites within the beta-2-microglobulin gene in mismatch repair-deficient colorectal cancers and adenomas

AbstractIn colorectal cancers (CRCs) with tumour mismatch repair (MMR) deficiency, genes involved in the host immune response that contain microsatellites in their coding regions, including beta-2-microglobulin (B2M), can acquire mutations that may alter the immune response, tumour progression and prognosis. We screened the coding microsatellites withinB2M for somatic mutations in MMR-deficient CRCs and adenomas to determine associations with tumour subtypes, clinicopathological features and survival. Incident MMR-deficient CRCs from Australasian Colorectal Cancer Family Registry (ACCFR) and the Melbourne Collaborative Cohort Study participants (n  = 144) and 63 adenomas from 41 MMR gene mutation carriers from the ACCFR were screened for somatic mutations within five coding microsatellites ofB2M. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival byB2M mutation status were estimated using Cox regression, adjusting for age at CRC diagnosis, sex, AJCC stage and grade.B2M mutations occurred in 30 (20.8%) of the 144 MMR-deficient CRCs (29% of theMLH1-methylated, 17% of the Lynch syndrome and 9% of the suspected Lynch CRCs). NoB2M mutations were identified in the 63 adenomas tested.B2M mutations differed by site, stage, grade and lymphocytic infiltration although none reached statistical significance (p  >  0.05). The HR for overall survival forB2M mutated CRC was 0.65 (95% CI 0.29 –1.48) compared withB2M wild-type. We observed differences inB2M...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research