Author of

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  P3.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 978)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27648

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    P3.12-09 - Smad4 Mutation Confers Acquired Neuroendocrine Phenotype in Transformation of Lung Adenocarcinoma to Small Cell Lung Cancer (ID 13104)

    12:00 - 13:30  |  Presenting Author(s): Jie Zhang
    • Abstract

    Background
    

    Along with the widely use of EGFR-TKI therapy, transformation from lung adenocarcinoma (LAC) to small cell lung cancer (SCLC) has been recognized and accepted as a reason of drug resistance , but the mechanism remains unclear .

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    At first, we detected mutated genes in LAC and SCLC component from 9 combined SCLC cases independently by NGS, and analyzed the gene expression in pairs to find the targeted genes. And then, we knocked out the putative gene in HCC827 cell line by CRISPR/Cas9 to detect the changes of classic neuroendocrine markers (CgA, Syn, CD56).

    4c3880bb027f159e801041b1021e88e8 Result
    

    A high mutation rate of Smad4 gene is observed in SCLC component from 9 combined SCLC cases (66.7%, 6/9, Figure 1A), which is much higher than that in pure SCLC (1.8%, available on http://www.cbioportal.org) samples. HCC827-Smad4^-/- cell line is successfully established (Figure 1B), and by IHC assay, the expression of Syn is obviously enhanced in HCC827-Smad4^-/- cells when compared with HCC827-GFP cells (Figure 1C).
    

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    The dysfunction of Smad4 protein confers the neuroendocrine phenotype of LAC, which plays a potential role in transformation to SCLC.

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