Details

Autor(en) / Beteiligte

• Pritchard, Colin C
• Salipante, Stephen J
• Koehler, Karen
• Smith, Christina
• Scroggins, Sheena
• Wood, Brent
• Wu, David
• Lee, Ming K
• Dintzis, Suzanne
• Adey, Andrew
• Liu, Yajuan
• Eaton, Keith D
• Martins, Renato
• Stricker, Kari
• Margolin, Kim A
• Hoffman, Noah
• Churpek, Jane E
• Tait, Jonathan F
• King, Mary-Claire
• Walsh, Tom

Titel

Validation and Implementation of Targeted Capture and Sequencing for the Detection of Actionable Mutation, Copy Number Variation, and Gene Rearrangement in Clinical Cancer Specimens

Ist Teil von

• The Journal of molecular diagnostics : JMD, 2014, Vol.16 (1), p.56-67

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Recent years have seen development and implementation of anticancer therapies targeted to particular gene mutations, but methods to assay clinical cancer specimens in a comprehensive way for the critical mutations remain underdeveloped. We have developed UW-OncoPlex, a clinical molecular diagnostic assay to provide simultaneous deep-sequencing information, based on >500× average coverage, for all classes of mutations in 194 clinically relevant genes. To validate UW-OncoPlex, we tested 98 previously characterized clinical tumor specimens from 10 different cancer types, including 41 formalin-fixed paraffin-embedded tissue samples. Mixing studies indicated reliable mutation detection in samples with ≥10% tumor cells. In clinical samples with ≥10% tumor cells, UW-OncoPlex correctly identified 129 of 130 known mutations [sensitivity 99.2%, (95% CI, 95.8%–99.9%)], including single nucleotide variants, small insertions and deletions, internal tandem duplications, gene copy number gains and amplifications, gene copy losses, chromosomal gains and losses, and actionable genomic rearrangements, including ALK-EML4 , ROS1 , PML-RARA , and BCR-ABL . In the same samples, the assay also identified actionable point mutations in genes not previously analyzed and novel gene rearrangements of MLL and GRIK4 in melanoma, and of ASXL1 , PIK3R1 , and SGCZ in acute myeloid leukemia. To best guide existing and emerging treatment regimens and facilitate integration of genomic testing with patient care, we developed a framework for data analysis, decision support, and reporting clinically actionable results.