Study Finds New Whole-Exome Sequencing Test Accurately Identifies Actionable Mutations
Exome Cancer Test v1.0 (EXaCT-1), a new whole-exome sequencing test developed by the Englander Institute for Precision Medicine at Weill Cornell Medicine, detected mutations that guide precision cancer treatment with over 95% accuracy, according to a study by Rennert et al published in Genomic Medicine. The test may also be beneficial for evaluating germline alterations and determining how responsive a patient is to immunotherapy, according to the study authors, the investigators concluded.
Study Methodology
EXaCT-1 uses the HaloPlex Target Enrichment System for target amplification, followed by sequencing on the Illumina system of tumor and matched constitutional control DNA. The quality, depth-of-coverage, and accuracy metrics of the new whole-genome/exome sequencing assay was established using HapMap DNA specimens and 57 normal/tumor samples positive for any mutation in 5 genes: KRAS, BRAF, JAK2, EGFR, and HER2/neu.
The researchers then analyzed 337 prospective tumor specimens, primary and metastatic, from patients with advanced cancer.
Study Findings
The researchers 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 tumors. Extensive sensitivity studies identified limits of the detection threshold for somatic point/indel mutations and copy-number alterations.
A prospective analysis of 337 tumor specimens revealed mutations in clinically relevant genes in 82% of the tumors.
“We have developed EXaCT-1, an accurate, sensitive, and specific method for identifying actionable mutations that guide precision cancer treatment, providing additional genomic sequencing options for precision medicine cancer care. The study also provides a paradigm for whole-exome sequencing (WES) validation using a broad selection of tumor types and to our knowledge providing the largest comprehensive study of WES for cancer care in the clinical laboratory,” concluded the study authors.
Mark A. Rubin, MD, of Weill Cornell Medical College, is the corresponding author of this study article.
Funding for this study was provided by Starr Cancer Consortium, the National Cancer Institute, Prostate Cancer Foundation, Department of Defense, Hirschl Trust, and the Damon Runyon Cancer Research Foundation.
The study authors reported no conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
