TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome

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Date: April 19, 2018

Authors:

Aaron M. Elliott, Bing Li, Carey Cullinane, Carin R. Espenschied, Chia-Ling Gau, PhD, DABMG, Daneil Chen, David Margileth, Ellen Totten, Hsiao-Mei Lu, Huma Rana, Huy Vuong, Jayne Hoo, Jonathan Terdiman, Lavinia Dobrea, Lawrence Wagman, Lisa Uyeda, Michael J. Hall, Mike Janicek, Monalyn Umali, Navanjot Batth, Pei Tsai, Phillip N. Gray, Sandra Brown, Sara Willett, Savita Ries, Sitao Wu, Swati Shah, Theodora Ross, Wenbo Mu

Journal: Oncotarget

Journal Volume: 9

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Abstract

The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2, MSH6, MLH1, PMS2 and EPCAM. Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.