Author of

• 12769

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  P3.18 - Poster Session 3 - Pathology (ID 177)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12788

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    P3.18-019 - Profiling of Actionable Alterations in Lung Adenocarcinoma (ID 3095)

    09:30 - 09:30  |  Author(s): K. Prabhash
    • Abstract

    Background
    Lung cancer remains a major unmet medical need in India and worldwide. About 63,000 new cases are diagnosed each year in India with deaths estimated at approximately 52,000, accounting for about 8% of all cancer deaths.Currently available cytotoxic chemotherapy is clearly inadequate for treatment of lung cancer. Therapies targeting the EGFR and ALK tyrosine kinases have proven effective for lung adenocarcinoma patients whose tumors harbor genomic alterations of the EGFR and ALK genes, respectively. However, most lung adenocarcinomas do not harbor these alterations and are not responsive to the relevant treatments. Hence, identification of mutationally activated oncogenes in lung cancer could result in additional therapeutic targets for this deadly disease.

    Methods
    676 exons from 196 were capturedin a discovery set of 125 Indian lung adenocarcinomasamples (FFPE blocks)using microfluidics based RainDance RDT-1000platform. The libraries were multiplexed and sequenced on Illumina Genome Analyser IIx. to obatin 1000X coverage per samples per base.Sequencing data were analysedusing in-house customized informtaicspipeline to identify potential driver alterations. 39 significantly altered mutations (novel and those known to be altered in NSCLC)were genotyped in an additional validation set of 300lung adeomcarcinomasamples using Sequenom MassArray.

    Results
    This is the firstreport of most comprehensive spectrum of alterations in 300Indian lung adenocarcinoma patients. We have identifiedmutation in genes previously reported as significantly mutated in lung adenocarcinoma: TP53, EGFR, KRAS, ERBB2, PIK3CA and NRASalong with previously unknown mutation incidence in AKT1 and NF2. In addition, we identified statistically recurrent mutations in the members of the fibroblast growth factor receptor familyin a subset of NSCLC tumors.

    Conclusion
    We identifyFGFRfamilyas a potential therapeutic target, a new avenue of investigation for the treatment of lung adenocarcinomas of Indian origin. This study also establishes a significant technological advancement for using cutting edge technologies on FFPE clinical specimens for high definition genomics, which has been a major impediment. in clinical research.In over all, this study enhances our understanding of the genomic complexity and heterogeneity underlying NSCLC tumors.