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S. Finn

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    MINI 13 - Genetic Alterations and Testing (ID 120)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI13.08 - Targetable Genomic Aberrations in Squamous Cell Lung Cancer (SCC): A Report from the Lung Cancer Genomics Ireland (LCGI) Study (ID 766)

      10:45 - 12:15  |  Author(s): S. Finn

      • Abstract
      • Presentation
      • Slides

      The prognosis of lung SCC continues to be poor with no molecularly targeted agents specifically developed for its treatment. LCGI aims to identify potential targetable oncogenes in lung SCC.

      The LCGI study is being carried out in 500 patients with surgically resected lung SCC, treated at St James’s University Hospital and Beaumont University Hospital, Dublin. We used the platform of Sequenom’s MassArray to perform genotyping for accustomed panel of 258 somatic hotspot mutations in 49 genes including genes in the MAPK and PI3K pathways. We also evaluated FGFR1 amplification by fluorescence in situ hybridization (FISH) and MET protein expression by immunohistochemistry (IHC).

      Lung SCCs from 258 patients have been tested by Sequenom MassArray to date. Lung SCCs from 150 patients have been evaluated for MET protein expression and 89 for FGFR1 amplification. 163 (63.2%) patients were male. The median age of the cohort was 68. The majority of patients were either current (39.5%) or former (58.1%) smokers at the time of diagnosis. 138 (53.5%) were stage I, 87 (33.7%) were stage II, and 33 (12.8%) were stage III SCCs. At least one aberrant, potentially targetable oncogene was identified in the SCC of 101 (39.1%) patients (see Table). The presence of PIK3CA or KRAS mutations, or FGFR1 amplification did not have a statistically significant impact on median overall survival or recurrence-free survival. However, the presence of two or more aberrations in driver oncogenes in a tumor (patients, n=19) was associated with a worse median overall survival compared to patients with either a single driver aberration (p=0.04) or no aberrations (p<.01). Table: Frequency of driver mutations in LCGI compared to The Cancer Genome Atlas (TCGA) study

      Mutation LCGI (n=258) TCGA (n=178)
      FGFR1 amp (n=89) 13 % 16.8 %
      PIK3CA 15.1 % 10.1 %
      KRAS 6.5 % 0.6 %
      PTPN11 3.5 % 1.7 %
      STK11 3.1 % 1.7 %
      MYC 1.9 % 0.0 %
      NRAS 1.6 % 0.0 %
      BRAF 1.2 % 3.9 %
      HRAS 1.6 % 1.7 %
      CTNNB1 1.5 % 1.7 %
      FBXW7 1.5 % 3.4 %
      MET Overexpression (n=150) 1.3 % NA
      EGFR 0.9 % 2.8 %
      AKT1 0.4 % 0.6 %
      CDK4 0.4 % 0.0 %
      GNA11 0.4 % 0.6 %
      MAP2K1 0.4 % 0.6 %
      DDR2 0 % 1.1 %

      39.1% of lung SCC patients have an aberrant, potentially targetable driver oncogene in their tumor. The presence of two or more aberrant oncogenes is a poor prognostic factor in lung SCC. These findings can be used to guide clinical trials in lung SCC.

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