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M. Noguchi



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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
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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. Noguchi

      • 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.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-018 - ECT2 overexpression and gene alteration are associated with the outcome of early-stage lung adenocarcinoma (ID 1761)

      09:30 - 09:30  |  Author(s): M. Noguchi

      • Abstract

      Background
      Background: In order to evaluate gene abnormality in lung adenocarcinoma at an early stage, genomic DNAs of six in situ adenocarcinomas (Ad) and nine small but invasive adenocarcinomas (INVAd) were examined by array-comparative genomic hybridization. Finally, 3q26 was detected as a significantly amplified region in INVAd relative to in situ Ad. Among the genes located at 3q26, we selected the epithelial cell transforming sequence 2 oncogene (ECT2) and examined it for abnormality in lung Ad, since ECT2 is related to Rho-specific exchange factors and cell cycle regulators, and is also thought to have an important role in the regulation of cytokinesis.

      Methods
      Methods: The clinical implications of ECT2 abnormality were examined by quantitative real-time genomic PCR (qPCR) and immunohistochemistry (IHC) using 158 cases of varies types of LAd, resected at Tsukuba University Hospital. The results were verified by cDNA microarray and 10k SNP array using another set of early-stage LAds, resected at the National Cancer Center Hospital.

      Results
      Results: qPCR and IHC analyses revealed overexpression of ECT2 in INVAd, and this was correlated with the MIB-1 index. ECT2 overexpression was significantly associated with lymph node metastasis, pathological stage, vascular invasion and the histological subtype of Ad. Patients with LAd overexpressing ECT2 showed an unfavorable outcome in terms of both disease-free and overall survival (Figure). These results were verified using another set of 144 early-stage Ads resected at the National Cancer Center Hospital. Figure 1

      Conclusion
      Conclusion: ECT2 is a new marker that can be used for prognostication of patients with early-stage LAd.