Germline and Tumor Sequencing as a Diagnostic Tool to Resolve Suspected Lynch Syndrome

People who develop mismatch repair (MMR) deficient cancer in the absence of a germline MMR gene pathogenic variant or somatic hypermethylation of the MLH1 gene promoter are classified as having suspected Lynch syndrome (SLS). Germline whole genome sequencing (WGS) and targeted and genome-wide tumor sequencing was applied to identify the underlying cause of tumor MMR-deficiency in SLS. Germline WGS was performed on 14 cancer-affected people with SLS, including two sets of first-degree relatives. Germline pathogenic variants, including complex structural rearrangements and non-coding variants, were assessed for the MMR genes.

Source: Journal of Molecular Diagnostics - December 28, 2020 Category: Pathology Authors: Bernard J. Pope, Mark Clendenning, Christophe Rosty, Khalid Mahmood, Peter Georgeson, Jihoon E. Joo, Romy Walker, Ryan A. Hutchinson, Harindra Jayasekara, Sharelle Joseland, Julia Como, Susan Preston, Amanda B. Spurdle, Finlay A. Macrae, Aung K. Win, John Tags: Regular Article Source Type: research