Author of

• 14490

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  P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14501

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    P2.04-011 - Whole-Genome Copy Number Analyses of NSCLC Tumors Reveal Aberrations Associated With EGFR Mutations and May Have Prognostic Impact (ID 1504)

    09:30 - 09:30  |  Author(s): G. Nilsen
    • Abstract
    • Slides

    Background:
    Knowledge about genetic alterations in Non-Small Cell Lung Cancer (NSCLC) has given us a significant insight in the biology of these tumors. It is of great clinical importance with consequences for the patients, and DNA mutations and translocations are currently targets for therapy. Aberrations in DNA copy number are frequent events in NSCLC tumors and important in tumorogenesis. In this present study we want to investigate how the copy number changes varies between different subgroups of NSCLC tumors based on the patients’ smoking status, histology or EGFR-, KRAS- and TP53 mutations. The DNA copy number data will be integrated with global mRNA expression to study the cis-associated mRNA expression changes. Last, we want to investigate whether genomic events, like specific copy number changes or the complex arm-wise aberration index (CAAI), have prognostic impact in patients with NSCLC.
    
    Methods:
    In this study we have included 200 patients with operable NSCLC tumors. Copy number data were obtained by using the Affimetrix Genome-wide human SNP array 6.0. Histopathological information, EGFR-, KRAS- and TP53 mutation status were determined and clinical information and follow-up data was obtained for all patients. The mRNA expression was determined by the Agilent 60K mRNA expression array on a subset of 117 patients. The data was analyzed by using bioinformatic tools like ASCAT and integration of the mRNA data and the survival analyses are on-going.
    
    Results:
    Preliminary results have shown that copy number aberrations are frequent events in NSCLC tumors, consistent with previous reports. We have identified that the copy number patterns differ between adenocarcinomas and squamous cell carcinomas, and between tumors from patients with different smoking history. However, the largest differences were found between the EGFR-mutated adenocarcinomas compared with EGFR wildtype tumors, where we identified a specific pattern of copy number changes in the tumors that harbour EGFR mutation. These changes were mainly located at chromosome arm 1p, 2p, 3q, 5q, 7, 12 and 13. Preliminary analyses have also identified specific copy number aberrations with prognostic significance.
    
    Conclusion:
    Copy number aberrations are frequent in NSCLC tumors and may have great impact on gene expression and give us valuable prognostic information. EGFR-mutated adenocarcinomas have a specific pattern of copy number changes, which provides new insight of the biology of these tumors.
    
    

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