Research Papers:

TumorNext: A comprehensive tumor profiling assay that incorporates high resolution copy number analysis and germline status to improve testing accuracy

Phillip N. Gray _, Huy Vuong, Pei Tsai, Hsaio-Mei Lu, Wenbo Mu, Vickie Hsuan, Jayne Hoo, Swati Shah, Lisa Uyeda, Susanne Fox, Harshil Patel, Mike Janicek, Sandra Brown, Lavinia Dobrea, Lawrence Wagman, Elizabeth Plimack, Ranee Mehra, Erica A. Golemis, Marijo Bilusic, Matthew Zibelman and Aaron Elliott

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Oncotarget. 2016; 7:68206-68228. https://doi.org/10.18632/oncotarget.11910

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Phillip N. Gray1, Huy Vuong1, Pei Tsai1, Hsaio-Mei Lu1, Wenbo Mu1, Vickie Hsuan1, Jayne Hoo1, Swati Shah1, Lisa Uyeda1, Susanne Fox1, Harshil Patel1, Mike Janicek2, Sandra Brown3, Lavinia Dobrea3, Lawrence Wagman3, Elizabeth Plimack4, Ranee Mehra4, Erica A. Golemis4, Marijo Bilusic4, Matthew Zibelman4, Aaron Elliott1

1Ambry Genetics, Aliso Viejo, CA, 92656, USA

2Arizona Oncology, Scottsdale, AZ, 85258, USA

3St. Joseph Health, Orange, CA, 92868, USA

4Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

Correspondence to:

Phillip N. Gray, email: [email protected]

Keywords: tumor profiling, actionable mutations, next generation sequencing, copy number variants, germline mutations

Received: June 16, 2016     Accepted: August 26, 2016     Published: September 08, 2016


The development of targeted therapies for both germline and somatic DNA mutations has increased the need for molecular profiling assays to determine the mutational status of specific genes. Moreover, the potential of off-label prescription of targeted therapies favors classifying tumors based on DNA alterations rather than traditional tissue pathology. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext, which can detect single nucleotide variants, small insertions and deletions in 142 genes that are frequently mutated in somatic and/or germline cancers. TumorNext also detects gene fusions and structural variants, such as tandem duplications and inversions, in 15 frequently disrupted oncogenes and tumor suppressors. The assay uses a matched control and custom bioinformatics pipeline to differentiate between somatic and germline mutations, allowing precise variant classification. We tested 170 previously characterized samples, of which > 95% were formalin-fixed paraffin embedded tissue from 8 different cancer types, and highlight examples where lack of germline status may have led to the inappropriate prescription of therapy. We also describe the validation of the Affymetrix OncoScan platform, an array technology for high resolution copy number variant detection for use in parallel with the NGS panel that can detect single copy amplifications and hemizygous deletions. We analyzed 80 previously characterized formalin-fixed paraffin-embedded specimens and provide examples of hemizygous deletion detection in samples with known pathogenic germline mutations. Thus, the TumorNext combined approach of NGS and OncoScan potentially allows for the identification of the “second hit” in hereditary cancer patients.

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