Westwood, A, Glover, A, Hutchins, G et al. (9 more authors) (2019) Additional loss of MSH2 and MSH6 expression in sporadic deficient mismatch repair colorectal cancer due to MLH1 promoter hypermethylation. Journal of Clinical Pathology, 72 (6). pp. 443-447. ISSN 0021-9746
Abstract
Colorectal cancer (CRC) is common with 3% of cases associated with germline mutations in the mismatch repair pathway characteristic of Lynch syndrome (LS). The UK National Institute for Health and Care Excellence recommends screening for LS in all patients newly diagnosed with CRC, irrespective of age. The Yorkshire Cancer Research Bowel Cancer Improvement Programme includes a regional LS screening service for all new diagnoses of CRC. In the first 829 cases screened, 80 cases showed deficient mismatch repair (dMMR) including four cases showing areas with loss of expression of all four mismatch repair proteins by immunohistochemistry. The cases demonstrated diffuse MLH1 loss associated with BRAF mutations and MLH1 promoter hypermethylation in keeping with sporadic dMMR, with presumed additional double hit mutations in MSH2+/−MSH6 rather than underlying LS. Recognition and accurate interpretation of this unusual phenotype is important to prevent unnecessary referrals to clinical genetics and associated patient anxiety.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019, Author(s) (or their employer(s)). No commercial re-use. See rights and permissions. Published by BMJ. This is an author produced version of a paper published in Journal of Clinical Pathology. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 Jan 2019 11:01 |
Last Modified: | 07 Jun 2019 14:11 |
Status: | Published |
Publisher: | BMJ Publishing Group |
Identification Number: | 10.1136/jclinpath-2018-205687 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:141613 |
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