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; Aaron M. Elliott

doi:10.18632/oncotarget.24854

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 DobreaLawrence Wagman, Huma Rana, Michael J. Hall, Theodora Ross, Jonathan Terdiman, Carey Cullinane, Savita Ries, Ellen Totten, Aaron M. Elliott

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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.

Original language	English (US)
Pages (from-to)	20304-20322
Number of pages	19
Journal	Oncotarget
Volume	9
Issue number	29
DOIs	https://doi.org/10.18632/oncotarget.24854
State	Published - Apr 17 2018

Keywords

Colorectal cancer
Lynch syndrome
Microsatellite instability
Mismatch repair deficiency
Next generation sequencing

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.24854

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Gray, P. N., Tsai, P., Chen, D., Wu, S., Hoo, J., Mu, W., Li, B., Vuong, H., Lu, H. M., Batth, N., Willett, S., Uyeda, L., Shah, S., Gau, C. L., Umali, M., Espenschied, C., Janicek, M., Brown, S., Margileth, D., ... Elliott, A. M. (2018). 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, 9(29), 20304-20322. https://doi.org/10.18632/oncotarget.24854

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, Phillip N.; Tsai, Pei; Chen, Daniel et al.
In: Oncotarget, Vol. 9, No. 29, 17.04.2018, p. 20304-20322.

Research output: Contribution to journal › Article › peer-review

Gray, PN, Tsai, P, Chen, D, Wu, S, Hoo, J, Mu, W, Li, B, Vuong, H, Lu, HM, Batth, N, Willett, S, Uyeda, L, Shah, S, Gau, CL, Umali, M, Espenschied, C, Janicek, M, Brown, S, Margileth, D, Dobrea, L, Wagman, L, Rana, H, Hall, MJ, Ross, T, Terdiman, J, Cullinane, C, Ries, S, Totten, E & Elliott, AM 2018, '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, vol. 9, no. 29, pp. 20304-20322. https://doi.org/10.18632/oncotarget.24854

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title = "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",

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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AU - Wu, Sitao

AU - Hoo, Jayne

AU - Mu, Wenbo

AU - Li, Bing

AU - Vuong, Huy

AU - Lu, Hsiao Mei

AU - Batth, Navanjot

AU - Willett, Sara

AU - Uyeda, Lisa

AU - Shah, Swati

AU - Gau, Chia Ling

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AU - Janicek, Mike

AU - Brown, Sandra

AU - Margileth, David

AU - Dobrea, Lavinia

AU - Wagman, Lawrence

AU - Rana, Huma

AU - Hall, Michael J.

AU - Ross, Theodora

AU - Terdiman, Jonathan

AU - Cullinane, Carey

AU - Ries, Savita

AU - Totten, Ellen

AU - Elliott, Aaron M.

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N2 - 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.

AB - 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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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

Abstract

Keywords

ASJC Scopus subject areas

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