Author of

• 11543

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  P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

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

  • 11570

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    P2.06-027 - Low frequency KRAS mutations in colorectal cancer patients and the presence of multiple mutations in oncogenic drivers in non-small cell lung cancer patients (ID 2401)

    09:30 - 09:30  |  Author(s): P. Brohawn
    • Abstract

    Background
    Intra-tumor heterogeneity can confound mutational status in oncodriver genes and challenge targeted cancer therapy strategies. Ultra-deep sequencing can detect low-frequency and expanded clonal mutations in primary tumors to better inform treatment decisions

    Methods
    KRAS coding exons in 61 treatment-naïve colorectal cancer (CRC) tumors were sequenced, along with KRAS, EGFR, ALK, and MET in lung tumors from 3 Chinese non-small cell lung cancer (NSCLC) patients

    Results
    Forty-two percent of CRC patients (28/61) harbored mutations in the KRAS active domain, 12 patients harbored >1 mutation, and eleven patients (18%), of which 5 had frequencies <10%, were not detected by Sanger sequencing. Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were identified in one NSCLC patient. Multiple low frequency mutations in KRAS, EGFR, and MET and ALK gene copy number increases were found in a second NSCLC patient; a third NSCLC patient had EML4-ALK fusion with ALK, EGFR, and MET mutations. Multiple low frequency mutations occurred within individual gene in all three patients.

    Conclusion
    A complex pattern of intrinsic low frequency driver mutations in well-known tumor oncogenes may exist prior to treatment, potentially resulting in resistance to targeted therapies. Ultra-deep sequencing can characterize intra-tumor heterogeneity and identify such mutations which could ultimately impact treatment decisions.