Understanding the pathogenicity of noncoding mismatch repair gene promoter variants in Lynch syndrome

Liu, Qing, Thompson, Bryony A., Ward, Robyn L., Hesson, Luke B. and Sloane, Mathew A. (2016) Understanding the pathogenicity of noncoding mismatch repair gene promoter variants in Lynch syndrome. Human Mutation, 37 5: 417-426. doi:10.1002/humu.22971


Author Liu, Qing
Thompson, Bryony A.
Ward, Robyn L.
Hesson, Luke B.
Sloane, Mathew A.
Title Understanding the pathogenicity of noncoding mismatch repair gene promoter variants in Lynch syndrome
Journal name Human Mutation   Check publisher's open access policy
ISSN 1098-1004
1059-7794
Publication date 2016-05-01
Year available 2016
Sub-type Article (original research)
DOI 10.1002/humu.22971
Open Access Status Not Open Access
Volume 37
Issue 5
Start page 417
End page 426
Total pages 10
Place of publication Hoboken, NJ United States
Publisher John Wiley & Sons
Language eng
Abstract Lynch syndrome is the most common familial cancer condition that mainly predisposes to tumors of the colon and endometrium. Cancer susceptibility is caused by the autosomal dominant inheritance of a loss-of-function mutation or epimutation in one of the DNA mismatch repair (MMR) genes. Cancer risk assessment is often possible with nonsynonymous coding region mutations, but in many cases patients present with DNA sequence changes within noncoding regions, including the promoters, of MMR genes. The pathogenic role of promoter variants, and hence clinical significance, is unclear and this hinders the clinical management of carriers. In this review, we provide an overview of the classification of MMR gene variants, outline the laboratory assays and online resources that can be used to assess the causality of promoter variants in Lynch syndrome, and highlight some of the practical challenges of demonstrating the pathogenicity of these variants. In conclusion, we propose a guide that could be integrated into the current InSiGHT classification scheme to help determine if a MMR gene promoter variant is pathogenic.
Keyword Lynch syndrome
Cancer susceptibility
Noncoding variant
Promoter
5′ UTR
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Office of the Vice-Chancellor
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 29 Mar 2016, 11:54:03 EST by System User on behalf of Office of Deputy Vice-Chancellor (Research)