Clinical Validation of Whole Genome Sequencing for Cancer Diagnostics.

The Journal of Molecular Diagnostics : JMD
Paul RoepmanEdwin Cuppen

Abstract

Whole genome sequencing (WGS) using fresh-frozen tissue and matched blood samples from cancer patients may become the most complete genetic tumor test. With the increasing availability of small biopsies and the need to screen more number of biomarkers, the use of a single all-inclusive test is preferable over multiple consecutive assays. To meet high-quality diagnostics standards, we optimized and clinically validated WGS sample and data processing procedures, resulting in a technical success rate of 95.6% for fresh-frozen samples with sufficient (≥20%) tumor content. Independent validation of identified biomarkers against commonly used diagnostic assays showed a high sensitivity (recall; 98.5%) and precision (positive predictive value; 97.8%) for detection of somatic single-nucleotide variants and insertions and deletions (across 22 genes), and high concordance for detection of gene amplification (97.0%; EGFR and MET) as well as somatic complete loss (100%; CDKN2A/p16). Gene fusion analysis showed a concordance of 91.3% between DNA-based WGS and an orthogonal RNA-based gene fusion assay. Microsatellite (in)stability assessment showed a sensitivity of 100% with a precision of 94%, and virus detection (human papillomavirus), an ...Continue Reading

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Citations

May 22, 2021·The Journal of Molecular Diagnostics : JMD·Andrew C Nelson, Sophia L Yohe
Jul 14, 2021·Seminars in Cancer Biology·Vaidehi JobanputraOlivier Elemento
Aug 11, 2021·Nature Medicine·Joris van de HaarEmile E Voest
Sep 4, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hanneke van der WijngaartHenk M W Verheul

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