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

Mark Clendenning, Alvin Huang, Harindra Jayasekara, Marie Lorans, Susan Preston, Neil O’Callaghan, Bernard J. Pope, Finlay A Macrae, Ingrid M. Winship, Roger L Milne, Graham G. Giles, Dallas R. English, John L. Hopper, Aung K Win, Mark A. Jenkins, Melissa C. Southey, Christophe Rosty, Daniel D Buchanan, on behalf of Investigators from the Melbourne Collaborative Cohort Study and the Australasian Colorectal Cancer Family Registry Cohort

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12 Citations (Scopus)


In 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 within B2M 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 of B2M. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival by B2M 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 the MLH1-methylated, 17% of the Lynch syndrome and 9% of the suspected Lynch CRCs). No B2M 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 for B2M mutated CRC was 0.65 (95% CI 0.29–1.48) compared with B2M wild-type. We observed differences in B2M mutation status in MMR-deficient CRC by tumour subtypes, site, stage, grade, immune infiltrate and for overall survival that warrant further investigation in larger studies before B2M mutation status can be considered to have clinical utility.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalFamilial Cancer
Issue number1
Publication statusPublished - Jan 2018
Externally publishedYes


  • B2M
  • Colorectal cancer
  • Lynch syndrome
  • Microsatellite instability
  • Mismatch repair deficiency
  • MLH1 methylation

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