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  • Oncogenomics
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Genomic structure and mutational analysis of the human KIF1B gene which is homozygously deleted in neuroblastoma at chromosome 1p36.2

Oncogene volume 20, pages 5075–5083 (2001)Cite this article

Abstract

In order to clone candidate tumor suppressor genes whose loss contributes to the pathogenesis of neuroblastoma (NB), we performed polymerase chain reaction (PCR) screening using a high-density sequence tagged site-content map within a commonly deleted region (chromosome band 1p36) in 24 NB cell lines. We found a ∼480 kb homozygously deleted region at chromosome band 1p36.2 in one of the 24 NB cell lines, NB-1, and cloned the human homologue (KIF1B-β) of the mouseKif1B-β gene in this region. The KIF1B-β gene had at least 47 exons, all of which had a classic exon–intron boundary structure. Mouse Kif1B is a microtubule-based putative anterograde motor protein for the transport of mitochondria in neural cells. We performed mutational analysis of the KIF1B-β gene in 23 cell lines using 46 sets of primers and also an allelic imbalance (AI) analysis of KIF1B-β in 50 fresh NB samples. A missense mutation at codon 1554, GTG (Gly) to ATG (Met), silent mutations at codon 409 (ACG to ACA) and codon 1721 (ACC to ACT), and polymorphisms at codon 170, GAT (Asp) to GAA (Glu), and at codon 1087, TAT (Tyr), to TGT (Cys), were all identified, although their functional significances remain to be determined. The AI for KIF1B-β was slightly higher (38%) than those for the other two markers (D1S244, D1S1350) (35 and 32%) within the commonly deleted region (1p36). Reverse transcriptase-PCR analysis of the KIF1B-β gene revealed obvious expression in all NB cell lines except NB-1, although decreased expression of the KIF1B-β gene was found in a subset of early- and advanced-stage NBs. These results suggest that the KIF1B-β gene may not be a candidate for tumor suppressor gene of NB.

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Acknowledgements

We thank Mrs Soma and Mrs Soga for their excellent technical assistance. We express our appreciation to Professor Thomas A Look, Harvard Medical School, Dana-Farber Cancer Institute, for his generous gift of the NB cell lines. This work was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan and a Grant-in-Aid for Scientific Research on Priority Areas and Grant-in-Aid for Scientific Research (B) and (C) from the Ministry of Education, Science, Sports and Culture of Japan.

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  1. Department of Pediatrics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Hong Wei Yang, Ying Zhang Chen, Junko Takita, Hui Ying Piao & Yasuhide Hayashi

  2. Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba, 305-0074, Japan

    Ying Zhang Chen & Eiichi Soeda

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Yang, H., Chen, Y., Takita, J. et al. Genomic structure and mutational analysis of the human KIF1B gene which is homozygously deleted in neuroblastoma at chromosome 1p36.2. Oncogene 20, 5075–5083 (2001). https://doi.org/10.1038/sj.onc.1204456

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