Oncotarget. 2018 Apr 17;9(29):20304-20322. doi: 10.18632/oncotarget.24854. eCollection 2018 Apr 17.
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.
Gray PN1, Tsai P1, Chen D2, Wu S3, Hoo J3, Mu W3, Li B3, Vuong H3, Lu HM3, Batth N2, Willett S1, Uyeda L2, Shah S2, Gau CL2, Umali M2, Espenschied C2, Janicek M4, Brown S5, Margileth D5, Dobrea L6, Wagman L7, Rana H8, Hall MJ9, Ross T10, Terdiman J11, Cullinane C12, Ries S12, Totten E13, Elliott AM1.
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.
Lynch syndrome; colorectal cancer; microsatellite instability; mismatch repair deficiency; next generation sequencing