|Title||Development and validation of a whole-exome sequencing test for simultaneous detection of point mutations, indels and copy-number alterations for precision cancer care.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Rennert H, Eng K, Zhang T, Tan A, Xiang J, Romanel A, Kim R, Tam W, Liu Y-C, Bhinder B, Cyrta J, Beltran H, Robinson B, Mosquera JMiguel, Fernandes H, Demichelis F, Sboner A, Kluk M, Rubin MA, Elemento O|
|Journal||NPJ Genom Med|
We describe Exome Cancer Test v1.0 (EXaCT-1), the first New York State-Department of Health-approved whole-exome sequencing (WES)-based test for precision cancer care. EXaCT-1 uses HaloPlex (Agilent) target enrichment followed by next-generation sequencing (Illumina) of tumour and matched constitutional control DNA. We present a detailed clinical development and validation pipeline suitable for simultaneous detection of somatic point/indel mutations and copy-number alterations (CNAs). A computational framework for data analysis, reporting and sign-out is also presented. For the validation, we tested EXaCT-1 on 57 tumours covering five distinct clinically relevant mutations. Results demonstrated elevated and uniform coverage compatible with clinical testing as well as complete concordance in variant quality metrics between formalin-fixed paraffin embedded and fresh-frozen tumours. Extensive sensitivity studies identified limits of detection threshold for point/indel mutations and CNAs. Prospective analysis of 337 cancer cases revealed mutations in clinically relevant genes in 82% of tumours, demonstrating that EXaCT-1 is an accurate and sensitive method for identifying actionable mutations, with reasonable costs and time, greatly expanding its utility for advanced cancer care.
|Alternate Journal||NPJ Genom Med|
|PubMed Central ID||PMC5539963|
|Grant List||R01 CA116337 / CA / NCI NIH HHS / United States |
R01 CA194547 / CA / NCI NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States
Development and validation of a whole-exome sequencing test for simultaneous detection of point mutations, indels and copy-number alterations for precision cancer care.
Submitted by jpc2004 on February 5, 2020 - 4:58pm