Mutation Yield of a Custom 212-Gene Next-Generation Sequencing Panel for Solid Tumors: Clinical Experience of the First 260 Cases Tested Using the JAX ActionSeq™ Assay

Mol Diagn Ther. 2020 Feb;24(1):103-111. doi: 10.1007/s40291-019-00435-9.

Abstract

Objective: The study aimed to retrospectively evaluate the positive yield rate of a custom 212-gene next-generation sequencing (NGS) panel, the JAX ActionSeq™ assay, used in molecular profiling of solid tumors for precision medicine.

Methods: We evaluated 261 cases tested over a 24-month period including cancers across 24 primary tissue types and report on the mutation yield in these cases.

Results: Thirty-three of the 261 cases (13%) had no detectable clinically significant variants. In the remaining 228 cases (87%), we identified 550 clinically significant variants in 88 of the 212 genes, with four of fewer clinically significant variants being detected in 62 of 88 genes (70%). TP53 had the highest number of variants (125), followed by APC (47), KRAS (47), ARID1A (20), PIK3CA (20) and EGFR (18). There were 38 tier I and 512 tier II variants, with two genes having only a tier I variant, seven genes having both a tier I and tier II variant, and 79 genes having at least one tier II variant. Overall, the ActionSeq™ assay detected clinically significant variants in 42% of the genes included in the panel (88/212), 68% of which (60/88) were detected in more than one tumor type.

Conclusions: This study demonstrates that of the genes with documented involvement in cancer, only a limited number are currently clinically significant from a therapeutic, diagnostic and/or prognostic perspective.

MeSH terms

  • Biomarkers, Tumor*
  • Gene Expression Profiling / methods
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Mutation*
  • Neoplasms / diagnosis*
  • Neoplasms / genetics*
  • Precision Medicine* / methods
  • Prognosis
  • Transcriptome

Substances

  • Biomarkers, Tumor