Mutation Yield Of A 34-Gene Next-Generation Sequencing Test In Community-Based Tumor Samples
JOURNAL OF CLINICAL ONCOLOGY(2015)
Abstract
e22132 Background: Several targeted therapies have been approved for treatment of solid tumors. Identification of gene mutations associated with response to these targeted therapies is rapidly progressing. We developed and validated a 34-gene next-generation sequencing (NGS) panel and used this to test community-based samples sent for routine molecular testing for actionable gene mutations. Methods: A laboratory-developed NGS test on an Ion Torrent PGM sequencer was used to determine mutation profiles for 121 consecutive, de-identified FFPE tissue samples collected from patients diagnosed with melanoma (n = 31), lung (n = 27), colorectal (n = 33), and breast cancer (n = 30). NGS results were compared to those of the routine single-gene molecular tests. Results: Twenty-four (20%) samples had mutations detected by the originally requested tests, all of which were also detected by NGS. However, NGS detected at least 1 additional mutation not detected by the original test in 92 (76%) of the 121 samples. Of the additional mutations detected, 16 were actionable according to NCCN guidelines (3 BRAF [2 V600E and K483Q] in melanoma specimens; 2 KRAS [A146T and L19F], 2 BRAF [2 V600E] and 1 NRAS [Q61K] in colorectal cancer; and 2 EGFR [E746-A750 and R680Q] and 6 KRAS [A146T, G12C, G12V, Q22K, G12A and G13C] in lung cancer). Most of the additional mutations detected by NGS were in regions not covered by the routine molecular test(s); in the other cases, NGS may have provided greater sensitivity than the routine test. Overall, mutations were detected in 21 of the 34 genes included in the NGS panel, 17 of which were detected in multiple tumor types. The most frequently mutated gene was TP53 (64/121), but 83% (100/121) of the specimens harbored mutations in at least 1 gene other than TP53. Conclusions: This NGS assay frequently detected actionable mutations not identified by routine single-gene tests. These findings suggest that broader mutation profiling of solid tumors, as with the 34-gene NGS mutation panel, could provide additional information for treatment selection in a substantial proportion of cases.
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Key words
mutation yield,tumor samples,next-generation,community-based
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