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T. Goto

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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-072 - Comprehensive Genomic Alterations Identified by Next-Generation Sequencing of Lung Adenocarcinoma in Japanese Population (ID 4602)

      14:30 - 15:45  |  Author(s): T. Goto

      • Abstract

      Therapeutic approaches to lung cancer have shifted toward an emphasis on molecularly targeted therapy in genotypic subsets of patients (pts). Recent advances in next-generation sequencing (NGS) technologies have improved the ability to detect potentially targetable mutations. In this study, we aimed to analysis the genomic alterations of lung adenocarcinoma.

      A retrospective analysis of genomic data obtained from 99 archived formalin-fixed, paraffin-embedded samples from Japanese pts with lung adenocarcinoma were analyzed by NGS panel of 415 genes. Mutations and frequency of variants present in key oncogenic drivers for each pts were quantified. Fisher’s exact and t-tests were used to identify associations between genomic alterations and clinical characteristics.

      Sex: male 66 pts, female 33 pts. Smoking status: pack-year (PY) <30 (light smoker) 61 pts, PY≥30 (heavy smoker) 38 pts. Of all, the median number of mutation burden and actionable mutation were 13.5 (range 5-33) and 4 (range 1-19), respectively. The most frequent genomic alterations were EGFR (48%), TP53 (40%), CDKN2B (32%), RB1 (21%), and CDKN1B (19%). Representative genomic alterations with a FDA approved targeted therapy such as EGFR mutation (exon 19 deletion and exon 21 L858R), ALK fusion, ROS1 fusion, RET fusion, BRAF (V600E) mutation and, MET amplification were detected in 56 pts (R-GAs group) and the others were 43 pts (O-GAs group). In the O-GAs group, 39 pts had genomic alteration with targeted agent available on or off a clinical trial. As for smoking habit, R-GAs group were significantly associated with light smoker than O-GAs group (p<0.01). In R-GAs group, the median number of mutation burden and actionable mutation were 13 (range 5-20) and 4 (range 1-10), respectively. O-GAs group were significantly greater mutation burden and actionable mutation than R-GAs group (16.2 ± 6.8 vs. 12.3 ± 4.3, p<0.01; 6.5 ± 5.0 vs. 4.5 ± 2.2, p = 0.02, respectively). Of the 43 EGFR pts, there were no concurrent genomic alterations of ALK, ROS1, RET, BRAF and, MET. The most frequent concurrent mutations in EGFR were CDKN2B (37%), TP53 (28%), CDKN2A (23%), CDKN1B (21%), ARID1A (19%), RB1 (16%), and STK11 (16%). Among the EGFR cases, 38 (88%) pts had further genomic alteration with targeted agent available on or off a clinical trial excluding EGFR-TKI.

      With help of NGS, we found most pts might be treated by targeted therapies. Further study may emerge whether concurrent mutations, mutation burden and the number of actionable mutation are associated with survival outcome in lung adenocarcinoma.