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

Oncotarget
Phillip N GrayAaron M Elliott

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.

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Citations

Aug 9, 2019·Journal of Medical Genetics·Shuwei LiMaryHelen Black
Feb 1, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Monalyn U SalvadorMelissa Pronold
Oct 2, 2020·Clinical Chemistry·Dustin R LongStephen J Salipante
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Jan 13, 2021·International Journal of Molecular Sciences·Andrea Katharina LindnerRenate Pichler
Aug 17, 2021·Clinical and Translational Gastroenterology·Katherine DixonKasmintan A Schrader

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Methods Mentioned

BETA
biopsies
biopsy
PCR
Exome Sequencing
electrophoresis

Software Mentioned

OSCHP
Varscan2
OncoScan
Integrative Genomics Viewer
CASAVA
MSIsensor
Promega MSI Analysis System
GeneMapper
Lynch
TumorNext

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