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Z. Liang



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      153P - EGFR T790M co-exists with sensitive mutations in the same cell group in lung adenocarcinoma patients (ID 157)

      12:30 - 13:00  |  Author(s): Z. Liang

      • Abstract
      • Slides

      Background:
      EGFR TKI targeted therapy has improved lung adenocarcinoma patients’ prognosis tremendously, but almost all of patients inevitably develop acquired resistance to these agents, and EGFR T790M mutation is the major contributors. Previous work has shown that after TKI therapy, lung adenocarcinoma patients kept the sensitive mutation and acquired resistance mutation simultaneously by sequencing methods or in vitro cell line experiments. Whether the two different type mutations are in the same cell group or in two different cell groups is unknown.

      Methods:
      RNA in situ hybridization methods was employed to examined EGFR T790M and L858R mutation in lung adenocarcinoma cancer tissues which was obtained before and after TKI therapy. EGFR expression was examined by immunohistochemistry. EGFR mutation were detected by ARMS PCR methods.

      Results:
      Twenty-four patients were enrolled in this study which were divided into 3 groups. Group 1: 4 patients who had concurrent primary T790M and sensitive EGFR mutation. Group 2: 14 patients who acquired T790M mutation after receiving TKI therapy. Among them, 6 patients had biopsy tissues before and after TKI therapy. 8 patients only own tissues after TKI therapy. Group 3: 6 patients who had sensitive EGFR mutation and received TKI therapy, but re-biopsy tissues didn't have EGFR T790M. We found that the results of RNA ISH and ARMS PCR methods was identical in the majority of the examined tissues. Only one repeated biopsy tissue didn't identify EGFR T790M after TKI therapy by PCR in group 3, while the RNA ISH method detected T790M in this tissue which contain only 100 tumor cells. In the serial cut slides, we observed that T790M and L858R mutations were in the same cell group, not only in the primary resistance cases, but also in the acquired resistance cases. For the two cases which had tissues available after receiving third generation TKI therapy, we observed that T790M disappeared in the repeated biopsy specimen, leaving the sensitive mutation which existed from the beginning.

      Conclusions:
      EGFR sensitive mutation and T790M co-exist in the same cell groups. EGFR sensitive mutation is a trunk and drive mutation, while T790M is a passenger mutation during the treatment process by TKI therapy.

      Clinical trial identification:


      Legal entity responsible for the study:
      Peking Union Medical College Hospital

      Funding:
      Peking Union Medical College Youth Fund, the Fundamental Research Funds for the Central Universities (Project NO. 3332016002). Pathology Research Centre of the China Academy of Medical Sciences (Project No. 2016ZX310176-2)

      Disclosure:
      All authors have declared no conflicts of interest.

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