Author of

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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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    P3.02-001 - KIF5B/RET fusion gene in surgically-treated Japanese adenocarcinoma of the lung (ID 33)

    09:30 - 09:30  |  Author(s): S. Shimizu
    • Abstract

    Background
    Recently, a novel fusion gene resulting from linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). RET translocation was previously reported in thyroid cancer, as CCD6/RET translocation. However, the correlation between KIF5B/RET fusion gene status and clinicopathologic features of surgically-treated lung cancer has not been well characterized.

    Methods
    We have investigated KIF5B/RET fusion gene status in 371 surgically treated NSCLC (270 were adenocarcinoma and 101 were squamous cell carcinoma), 60 breast cancers, 11 metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma case at Nagoya City University Hospital. The fusion gene and CCD6/RET statuses were analyzed by RT-PCR based assay and direct sequencing. We have performed immunohistochemical (IHC) analysis using C-ternimal specific anti RET antibody (EPR2871, 1:250) (Epitomics Inc., Burlingame, CA, USA, n=86) with Dako linker kit using intercalated antibody-enhanced polymer (iAEP) method. Cytoplasm was stained either granular (G1) or diffuse (G2). G2 staining was defined as positive staining.

    Results
    We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.5 %) from the present study; all were mixed subtype adenocarcinomas and three were female and never-smokers. The fusion genes were exclusive with the other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4-ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. Of the 3 cases, 2 cases were KIF5B (exon15): RET (exon12) fusions with papillary dominant and 1 cases were KIF5B (exon22): RET (exon12) fusion with solid dominant adenocarcinoma. Matched normal lung tissues did not show translocation. In the present study, we did not detect CCD6/RET fusion genes. as a driver somatic mutation of lung adenocarcinomas. Although all 3 had positive IHC staining, 35/86 had more than 10% staining and 15/86 had more than 50% staining.

    Conclusion
    In the present study, we reported KIF5B/RET fusion genes as a possible new driver somatic mutation of lung adenocarcinomas. Cinico-pathological backgrounds of the KIF5B/RET fusion positive patients were similar with that of the EML4/ALK fusion positive patients. The chimeric oncogene might be as a promising molecular target for the personalized diagnosis and treatment of NSCLC. However, the chimeric oncogene might not be determined using IHC analysis.