Author of

• 11503

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  P2.03 - Poster Session 2 - Technology and Novel Development (ID 151)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11507

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    P2.03-004 - Clinical application of targeted deep sequencing as a molecular screening for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in never-smoking lung adenocarcinoma (ID 2170)

    09:30 - 09:30  |  Author(s): Y.S. Lee
    • Abstract

    Background
    The molecular screening is a key step to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. We investigated the clinical relevance of targeted next generation sequencing (NGS) as a molecular screening for EGFR-TKI therapy in never-smoking lung adenocarcinoma (NSLA).

    Methods
    We obtained DNA from 48 NSLA received gefitinib or erlotinib for their recurrent disease after surgery. The Sanger sequencing and peptide nucleic acid clamp polymerase chain reaction (PCR) were used to analyze EGFR, KRAS, BRAF and PIK3CA mutations. We analyzed ALK, RET and ROS1 rearrangements by fluorescent in situ hybridization or reverse transcriptase-PCR and quantitative real-time PCR. Finally, Ion Torrent NGS was performed in 31 cases harboring only EGFR exon 19 deletions (19DEL) or L858R mutation or none of above mutations.

    Results
    After excluding mutations other than EGFR 19DEL or L858R, samples were divided into 4 groups; 1) responders to EGFR-TKIs with only 19DEL or L858R (n=15); 2) primary resistance to EGFR-TKI with only 19DEL or L858R (n=4); 3) primary resistance to EGFR-TKI without any mutations (n=8); 4) responders to EGFR-TKI without any mutations (n=4). All conventionally detected mutations were confirmed with NGS. Additionally uncovered predictive mutations include; one PIK3CA E542K and one BRAF in group 2; two KRAS (G12V and G12D), one PIK3CA E542K and one concomitant PIK3CA and EGFR L858R in group 3; one EGFR 19DEL in group 4. Newly detected mutations were validated by Sanger sequencing.

    Conclusion
    Targeted NGS provided more accurate and clinically useful molecular classification of NSLA. It may improve personalized therapy for individual patients.