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Y. Miyagi



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    MINI 13 - Genetic Alterations and Testing (ID 120)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI13.09 - Next-Generation Sequencing Analysis of Driver Gene Mutations in Pleomorphic Carcinoma of the Lung (ID 1145)

      11:30 - 11:35  |  Author(s): Y. Miyagi

      • Abstract
      • Presentation
      • Slides

      Background:
      Research into druggable driver gene mutations in non-small cell lung cancer has identified several molecule-targeting agents that are clinically prescribed to inhibit tumor growth in adenocarcinoma. However, lung cancers without targeted driver gene mutations show poorly differentiated histologies and unfavorable prognoses without medication. Pleomorphic carcinoma, a lung cancer that includes a mixed conventional histology and sarcomatoid components, is an extremely aggressive tumor and rarely responds well to anticancer treatments. However, it has recently been reported that lung cancer with a sarcomatoid component contains the ALK gene rearrangement. Therefore, we used a next-generation sequencing (NGS) analysis of the driver gene mutations in pleomorphic carcinoma (PC) of the lung to identify druggable target molecules.

      Methods:
      We selected PCs from primary lung carcinomas by reviewing the records of 944 patients who had undergone surgical resection between 2007 and 2014. The Ion PGM™ NGS sequencer (Life Technology Inc., US) was used to identify known gene rearrangements in lung cancers by analyzing RNA with IonAmpliSeq™ RNA Lung FusionPanel® (Life Technology). With our original panel for targeted gene amplifications, the Ion PGM was also used to analyze nucleotide sequence of whole exons of 41 driver genes reported to be involved in lung cancers. The cases examined were also analyzed with ALK immunohistochemistry (ALK-IHC) using the N-Histofine® ALK Detection Kit (Nichirei Bioscience Inc., Tokyo, Japan) on sliced paraffin-embedded tumor specimens.

      Results:
      Twenty-one lung cancer specimens diagnosed as PC and frozen material from nine patients were available for NGS. The EML4ex6/ALKex20 fusion gene was detected in one case, which was also positive on ALK–IHC. No other fusion genes were detected. Another case, which was negative for the fusion gene, was weakly positivity on ALK–IHC, so an unbalanced 5¢/3¢-end ALK expression test is planned. Six of nine cases but not the ALK-fusion-positive cases showed driver gene mutations in TP53. We also found several somatic mutations in druggable genes in this study, which should be considered carefully to determine whether they are driver or passenger genes.

      Conclusion:
      Although a small number of PCs were examined in this study, the ALK fusion gene was detected, which indicates the frequency of ALK fusion might be high in PC. Other possible druggable gene mutations were also identified in PCs. Further cases must be investigated to understand the mutation status of driver genes in PC.

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