Journal article

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

Bernard Pope, Mark Clendenning, Christophe Rosty, Khalid Mahmood, Peter Georgeson, Jihoon Joo, Romy Walker, Ryan Hutchinson, Harindra Jayasekara, Sharelle Joseland, Julia Como, Susan Preston, Amanda Spurdle, Finlay Macrae, Aung Win, John Hopper, Mark Jenkins, Ingrid Winship, Daniel Buchanan

Cold Spring Harbor Laboratory | Published : 2020


Background People who develop mismatch repair (MMR) deficient cancer in the absence of a germline MMR gene pathogenic variant or hypermethylation of the MLH1 gene promoter in their tumor are classified as having suspected Lynch syndrome (SLS). We applied germline whole genome sequencing (WGS) and targeted and genome-wide tumor sequencing approaches to identify the underlying cause of tumor MMR-deficiency in SLS. Methods Germline WGS was performed on 14 cancer-affected people with SLS, including two sets of first-degree relatives. Tumor tissue was sequenced for somatic MMR gene mutations by targeted, whole exome sequencing or WGS. Germline pathogenic variants, including complex structural rea..

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