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Linfeng Li



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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-01 - BRAF V600 and Non-V600 Mutations in Chinese Lung Cancer (ID 13759)

      12:00 - 13:30  |  Author(s): Linfeng Li

      • Abstract
      • Slides

      Background

      BRAF gene mutation, especially V600E, was frequently mutated in cancer. Vemurafenib and dabrafenib has already been approved in melanoma as well as NSCLC and preclinical studies have demonstrated promising results in non-V600 NSCLC. But the landscape of BRAF non-V600 mutation in Chinsese lung cancer was rarely descripted.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      7,417 normal-paired samples from lung cancer patients were analyzed using hybridization capture-based next generation sequencing and alterations including single nucleotide variants (SNVs), short insertions/deletions (indels), copy number variations (CNVs) and structural variations (SV) were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      BRAF was altered in 1.8% (133 of 7,417) of all tumors. BRAF V600 (gain of function, GOF) and non-V600 mutations (GOF: G469V/R/E/A, K601N/E, L597V/R, T599dup/T599R, N486_P490del, L525R, and loss of function/LOF: D594N/G, N581S/I, G466V/A, K483E, G596R), has previously been reported to increase MEK/ERK activation, were detected in 52.3% (58/111) and 47.7% (53/111) of BRAF functional mutation patients. CNVs and SVs were both observed at a frequency of 0.9% (1/111). Two patients have two GOF mutations (V600E/T599R). We also found that 82.0% (91/111) of the BRAF functional mutation carriers also owned the other actionable or driver mutation, the most frequent one was TP53 (68.1%), then was EGFR (18.7%), KRAS/NRAS (14.3%), PIK3CA (11.0%) as well as CDKN2A/B (9.9%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      BRAF gene mutations, non-V600 especially, was extensively mutated in Chinese lung cancer. This work supports a broad profiling approach in lung cancers and suggests that non-V600E BRAF alterations represent a subgroup of lung cancers in which targeted therapy should be considered.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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