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  P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

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

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    P3.02-005 - Genome-wide Identification of Genes with Amplification and/or Fusion in Small Cell Lung Cancer (ID 1052)

    09:30 - 09:30  |  Author(s): M. Takenaka
    • Abstract

    Background
    Most of small cell lung cancer (SCLC) cases are diagnosed after metastatic spread of the diseases, and only 5% of SCLC patients survive beyond 5 years after diagnosis. Therefore, for the improvement of patients’ outcome in this disease, it is necessary to identify druggable targets that are activated by genetic alterations in SCLC cells.

    Methods
    To obtain a landscape of gross genetic alterations in SCLC, genome-wide copy number analysis and whole-transcriptome sequencing were performed in 58 and 42 SCLCs, respectively.

    Results
    Focal amplification of known oncogene loci, MYCL1 (1p34.2), MYCN (2p24.3), and MYC (8q24.21), was frequently and mutually exclusively detected. MYCL1 and MYC were co-amplified with other regions on either the same or the different chromosome in several cases. In addition, the 9p24.1 region was identified as being amplified in SCLCs without amplification of MYC family oncogenes. Notably, expression of the KIAA1432 gene in this region was significantly higher in KIAA1432 amplified cells than in non-amplified cells, and its mRNA expression showed strong correlations with the copy numbers. Thus, KIAA1432 is a novel gene activated by amplification in SCLCs. By whole-transcriptome sequencing, a total of 60 fusion transcripts, transcribed from 95 different genes, were identified as being expressed in SCLC cells. However, no in-frame fusion transcripts were recurrently detected in 2 SCLCs, and genes in the amplified regions, such as PVT1 neighboring MYC and RLF in MYCL1 amplicons, were recurrently fused with genes in the same amplicons or with those in different amplicons on either the same or different chromosome.

    Conclusion
    Amplification and fusion of several genes on chromosomes 1 and 8 were likely to occur simultaneously but not sequentially through chromothripsis in the development of SCLC. Amplification rather than fusion of genes was indicated to play an important role in its development.