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D. Liu



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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-002 - Is T790M Mutation A "Regulator" for EGFR Signal Pathway Not an Oncogene? (ID 3786)

      14:30 - 14:30  |  Author(s): D. Liu

      • Abstract
      • Slides

      Background:
      Threonine 790 is regarded as a “gatekeeper” to inhibit ATP from binding to EGFR Tyrosine kinase domain. T790M mutation could increase the affinity for ATP. About 30% de novo T790M mutation was detected in NSCLC patients and showed spatiotemporal heterogeneity and variation in individual NSCLC patients. We hypothesize that T790M mutation may be a “regulating” mechanism for EGFR signal transduction pathway and is probably cleared quickly by DNA repair system in healthy persons.

      Methods:
      Peripheral blood samples were taken from 50 healthy volunteers, 12 resectable lung adenocarcinoma (LADC), 100 advanced LADC (11/100 acquired resistance for gefitinib). A novel cSMART assay (circulating single-molecule amplification and resequencing technology, which counts single allelic molecules in plasma base on next generation sequencing) was performed for detection and quantitation of EGFR mutation in ctDNA from plasma. Matching tumor biopsy samples were obtained from 100 advanced LADC, the EGFR gene mutations were determined by amplification refractory mutation system (ARMS) -PCR analysis.

      Results:
      The sensitivity and specificity of cSMART plasma assay for EGFR L858R, 19del and T790M was showed in Table 1. The sensitivity and specificity for T790M was obviously lower (50.0% and 72.9% respectively). No L858R and 19del but 14.0% T790M DNA copies were found in plasma from 50 healthy volunteers, and only 1 copy T790M was detected. The T790M positive rate of resectable and advanced LADC patients were almost similar (33.3% and 28.0%) in plasma, 1 or 2 T790M copies were found in the resectable patients and varied from 1 to 622 T790M copies with an average of 34.0 in advanced LADC patients. Patients with acquired resistance to gefitinib, 45.4% harbored T790M with an average of 268.2 copies in plasma. All but one advanced patients harboring T790M mutation were accompanied with other EGFR mutations.

      Conclusion:
      T790M mutation may be of a “regulator” and has physiological function.

      Table 1 EGFR mutations detection by plasma cSMART assay and tumor samples ARMS-PCR in advanced LADC patients
      EGFR mutations Sensitivity Specificity
      L858R 91.7%(22/24) 100.0%(76/76)
      19Del 79.2%(19/24) 100.0%(76/76)
      T790M 50.0%(2/4) 72.9%(70/96)


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