Research Papers:

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

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

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Oncotarget. 2018; 9:20304-20322. https://doi.org/10.18632/oncotarget.24854

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Phillip N. Gray1, Pei Tsai1, Daniel Chen2, Sitao Wu3, Jayne Hoo3, Wenbo Mu3, Bing Li3, Huy Vuong3, Hsiao-Mei Lu3, Navanjot Batth2, Sara Willett1, Lisa Uyeda2, Swati Shah2, Chia-Ling Gau2, Monalyn Umali2, Carin Espenschied2, Mike Janicek4, Sandra Brown5, David Margileth5, Lavinia Dobrea6, Lawrence Wagman7, Huma Rana8, Michael J. Hall9, Theodora Ross10, Jonathan Terdiman11, Carey Cullinane12, Savita Ries12, Ellen Totten13 and Aaron M. Elliott1

1Advanced Genomic Services, Ambry Genetics, Aliso Viejo, CA 92656, USA

2Clinical Diagnostics Department, Ambry Genetics, Aliso Viejo, CA 92656, USA

3Bioinformatics Department, Ambry Genetics, Aliso Viejo, CA 92656, USA

4Cancer Genetic Risk Assessment Program, Arizona Oncology, Scottsdale, AZ 85258, USA

5Cancer Genetics Program, Saint Joseph of Orange, Orange, CA 92868, USA

6Oncology Research and Biospecimen Program, Saint Joseph of Orange, Orange, CA 92868, USA

7The Center for Cancer Prevention and Treatment, Saint Joseph of Orange, Orange, CA 92868, USA

8Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02461, USA

9Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia PA 19111, USA

10Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

11Department of Medicine – Gastroenterology, University of California San Francisco, San Francisco, CA 94115, USA

12Department of Pathology, Long Beach Memorial Medical Center, Long Beach, CA 90801, USA

13Advocate Medical Group, Park Ridge, Illinois 60068, USA

Correspondence to:

Phillip N. Gray, email: [email protected]

Keywords: Lynch syndrome; colorectal cancer; microsatellite instability; mismatch repair deficiency; next generation sequencing

Received: December 15, 2017     Accepted: March 06, 2018     Published: April 17, 2018


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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