Copy number variants in clinical next-generation sequencing data can define the relationship between simultaneous tumors in an individual patient

• Published in: Experimental and molecular pathology 2014-08, Vol.97 (1), p.69-73
• Main Authors: Sehn, Jennifer K., Abel, Haley J., Duncavage, Eric J.
• Format: Article
• Language: English
• Subjects: Biopsy, Large-Core Needle; Cancer; Carcinoma, Neuroendocrine - genetics; Carcinoma, Neuroendocrine - pathology; Copy number change; Deep sequencing; Gene Dosage; High-Throughput Nucleotide Sequencing - methods; Humans; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Metastasis; Molecular diagnostics; Neoplasms, Multiple Primary - genetics; Precision Medicine
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2014.05.008

Targeted next-generation sequencing (NGS) cancer panels have become a popular method for the identification of clinically predictive mutations in cancer. Such methods typically detect single nucleotide variants (SNVs) and small insertions/deletions (indels) in known cancer genes and can provide further information regarding diagnosis in challenging surgical pathology cases, as well as identify therapeutic targets and prognostically significant mutations. However, in addition to SNVs and indels, other mutation classes, including copy number variants (CNVs) and translocations, can be simultaneously detected from targeted NGS data. Here, as proof of methods, we present clinical data which demonstrate that targeted NGS panels can separate synchronous liver tumors based on CNV status, in the absence of distinct SNVs and indels. Such CNV-based analysis can be performed without additional cost using existing targeted cancer panel data and publically available software. •Clinical NGS of cancer specimens can be used to identify somatic mutations.•Identified somatic mutations provide clinically relevant information.•Mutation profiles can differentiate multiple primary tumors from metastases.•Copy number variants can be the only mutations that distinguish two tumors.•Copy number analysis should be included in clinical NGS assays.