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  P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26636

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    P1.13-45 - Coexistence of Activating BRAF and KRAS Mutations in Lung Cancer Patients (ID 13338)

    16:45 - 18:00  |  Presenting Author(s): yingyi Wang
    • Abstract
    • Slides

    Background
    

    Activating mutations in both KRAS and BRAF gene can stimulate mitogen-activated protein kinase (MAPK) signaling. So BRAF and KRAS mutations are generally mutually exclusive from each other, acting as an alternative oncogenic driver in NSCLC. There was occasionally case reports of coexistence of BRAF and KRAS mutations in colorectal cancer, lung squamous cell carcinoma. However, to our knowledge, there was no systemic studies in this area

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We retrospectively analyzed mutation profiling of 2000 consecutive lung cancer samples in our institute. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes).

    4c3880bb027f159e801041b1021e88e8 Result
    

    Sixty-three patients with activating BRAF mutation was analyzed in the study, including 48 lung adenocarcinoma, 3 squamous cell lung cancer, 1 lung adenosquamous cell carcinoma, 1 lung large cell carcinoma and 10 lung cancer patients with unspecified pathology. The most common BRAF mutation, BRAF V600E, was identified in 33 patients. BRAF Non-V600E mutation was identified in 30 patients, including G469A/V/R (7), D594G/N (6), K601E/N (6), G464V (3), G466A/V (3), G596R (2), K483E (1), N486_P490del (1) and N581S (1) mutations. Among the 63 patients, 8 (12.7%) had coexistence of activating KRAS mutation. Concurrence of activating KRAS mutation (G12A/D/S, G13D) was identified in 3 of the 30 patients with BRAF V600E mutations, with 2 of the 3 patients had previous EGFR-TKI treatment. The patient with KRAS G12S, G13D, and BRAF V600E mutation but without EGFR sensitive mutation had poor response to chemotherapy. On the contrary, activating KRAS mutation (G12D/V, G13D, A146V) was identified in 5 of the 33 patients with BRAF non-V600E mutation, with only one patient had EGFR-TKI sensitive mutation and previous EGFR-TKI treatment.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Coexistence of activating KRAS mutation is not uncommon in NSCLC patients with BRAF mutations, especially in patients with non-V600E mutations. Therefore, therapeutic choice for patients with BRAF non-V600E mutation need comprehensive consideration of companion mutations. Moreover, previous EGFR-TKI may increase the incidence of concurrence of generally mutually exclusive mutations.

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