An Update on the Pathogenesis of Lynch Syndrome: Recently Described Novel Molecular MechanismsAaron R. Huber*, D.O., Christa L. Whitney-Miller, Jennifer and J. Findeis-Hosey
Surgical Pathology Unit, University of Rochester Medical Center, USA
- *Corresponding Author:
- Aaron Ryan Huber
University of Rochester Medical Center
Surgical Pathology Unit 601 Elmwood Avenue
Rochester, NY 14618, USA
Tel: (585) 275-1702
Fax: (585) 276-2802
E-mail: [email protected]
Received date: November 06, 2013; Accepted date: November 18, 2013; Published date: November 26, 2013
Citation: Huber AR, Whitney-Miller DOCL, Jennifer, Findeis-Hosey J (2013) An Update on the Pathogenesis of Lynch Syndrome: Recently Described Novel Molecular Mechanisms. J Gastroint Dig Syst 3:151. doi: 10.4172/2161-069X.1000151
Copyright: © 2013 Whitney-Miller CL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Lynch syndrome, originally described in 1913 and previously known as hereditary nonpolyposis colorectal carcinoma syndrome, is the most common hereditary cancer syndrome. This syndrome is classically due to germline mutations in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2. The cancer risk for patients with Lynch syndrome is not limited to the colorectum; women with Lynch syndrome are at risk for endometrial cancer, and Lynch patients of both genders are at risk for other cancers as well. There are cases of cancers in families that meet the clinical criteria (Amsterdam and Bethesda criteria) for Lynch syndrome but do not have a mutation in the one of the four classic mismatch repair genes. For some time, there has been speculation that other mutations or mechanisms were responsible for a subset of Lynch syndrome patients; much research has gone into identifying those alternative mutations and mechanisms. Recently, EPCAM deletion, CHEK2 mutations, and germline MLH1 hypermethylation have been identified as alternative mutations that cause Lynch syndrome in mismatch repair-negative patients. This article reviews these novel mechanisms and mutations, their clinical significance, and the pathogenesis of these Lynch causing mutations.