Author of

• 12769

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  P3.18 - Poster Session 3 - Pathology (ID 177)

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

  • 12779

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    P3.18-010 - 5 Driver genes in Chinese Female Lung Adenocarcinoma (ID 1898)

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

    Background
    Currently, 5 driver genes (EGFR, K-RAS, B-RAF, ALK, RET) related to lung cancer have been widely explored and become new targets of NSCLC, however no report has been found in Chinese female lung adenocarcinoma, who were prone to EGFR mutations and therefore, are the targeted populations for TKIs therapy.

    Methods
    FFPE-tissues from 310 female lung adenocarcinoma adopted in Hunan province or Henan province between 2000 and 2012 were investigated. Oncogenic alterations in newly found 5 driver genes were analyzed. For EGFR, K-RAS and B-RAF mutation detection, ARMS was performed. The reverse transcription and real-time PCR were performed either to detect all ALK and RET fusions using primers specific to known rearrangement or to detect ALK and RET expression by primers specific to TK domain. Sequencing was further applied to confirm the subtypes of fusions.

    Results
    Among 310 samples, 149 (48.1%) EGFR mutations, 16 (5.2%) KRAS mutations, 0 (0%) BRAF mutations, 23 (7.4%) ALK fusions and 5 (1.6%) RET fusions were detected. Deletions in exon 19 and L858R in exon 21 account for the major EGFR mutations, representing 97 (65.1%) and 41 (27.5%), respectively. Only EML4-ALK fusion but no other ALK fusions were found. Further research demonstrated that cases (22, 95.6%) with high ALK expression were often accompanied by EML4-ALK fusion and poorly differentiated adenocarcinoma. Two RET fusions, namely, KIF5B-RET and CCDC6-RET were found, with 2 cases and 3 cases, respectively. The ratio of RET/ABL mRNA levels was significantly higher in CCDC6-RET samples with poorly differentiated adenocarcinoma. However, with KIF5B-RET fusion, the situation was more complex. Relatively high RET/ABL mRNA expression was detected in one KIF5B-RET sample with moderately differentiated adenocarcinoma, while no RET expression was detected in other two KIF5B-RET samples with highly differentiated adenocarcinoma.

    Conclusion
    This is the first research about the oncogenic alterations of 5 important driver genes in Chinese female lung adenocarcinoma, as well as the correlation between ALK fusion and ALK expression or between RET fusion and RET expression, thus laying good foundation for understanding the genetic mutation spectrum in female lung adenocarcinoma.