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Meiling Zhang



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    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.13-07 - CUX1-ALK: A Novel ALK Rearrangement That Responds to Crizotinib in Non-Small-Cell Lung Cancer (ID 12736)

      16:45 - 18:00  |  Author(s): Meiling Zhang

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer-related deaths worldwide. ALK rearrangement has been identified in 3% to 5% non-small-cell lung cancer (NSCLC) patients. The most common ALK rearrangement is EML4-ALK. Other rare ALK arrangements, such as KIF5IB-ALK and KLC-ALK, have also been identified that might be potential therapeutic targets, although the efficacy of ALK inhibitors on the majority of these rare ALK rearrangements has not been assessed in clinic.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this study, using comprehensive next-generation sequencing targeting 416 pan-cancer genes and introns of 16 genes frequently rearranged in cancer, we identified a novel CUX1-ALK fusion gene in a lung adenocarcinoma patient. The exact CUX1-ALK fusion transcript was determined via RNA-seq, and confirmed by RT-PCR. The oncogenic ability of CUX1-ALK fusion gene was further validated in 293T cells for the activation of ALK self-phosphorylation and downstream signaling pathways.

      4c3880bb027f159e801041b1021e88e8 Result

      After the detection of CUX1-ALK fusion gene, RNA-seq analysis of FFPE sections from the primary tumor specimen was applied to reveal a 97 nt fragment from CUX1 intron 8 inserted before the 53 nt position in ALK exon 20. Expression of the CUX1-ALK fusion protein in 293T cells confirmed the self-phosphorylation of the fusion protein and the activation of ALK downstream signaling pathways, including MAPK, JAK-STAT, and PI3K/AKT signaling pathways, which all could be inhibited by the addition of crizotinib. Furthermore, the patient showed a superior response to crizotinib with a progression-free survival of 20 months.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study provides the novel finding of CUX1-ALK fusion gene from NSCLC patient which could provide personalized treatment solutions for the maximum benefit to NSCLC patients.

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