Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

Cancers

Phillip N. Gray¹  Charles L.M. Dunlop²  Aaron M. Elliott² 

[1] Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656 USA;

关键词: next generation sequencing;    cancer panels;    target enrichment;    copy number;    molecular inversion probes;    somatic;    germline;   

DOI  :  10.3390/cancers7030837

来源: mdpi

【 摘 要 】

The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.