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Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line

Oncogene volume 19, pages 4302–4307 (2000)Cite this article

Abstract

Loss of heterozygosity of the distal region of chromosome 1p where tumor suppressor gene(s) might harbor is frequently observed in many human cancers including neuroblastoma (NBL) with MYCN amplification and poor prognosis. We have identified for the first time a homozygously deleted region at the marker D1S244 within the smallest region of overlap at 1p36.2-p36.3 in two NBL cell lines, NB-1 and NB-C201 (MASS-NB-SCH1), although our genotyping has suggested the possibility that both lines are derived from the same origin. The 800-kb PAC contig covering the entire region of homozygous deletion was made and partially sequenced (about 60%). The estimated length of the deleted region was 500 kb. We have, thus far, identified six genes within the region which include three known genes (DFF45, PGD, and CORT) as well as three other genes which have been reported during processing our present project for the last 3½ years (HDNB1/UFD2, KIAA0591F/KIF1B-β, and PEX14). They include the genes related to apoptosis, glucose metabolism, ubiquitin-proteasome pathway, a neuronal microtubule-associated motor molecule and biogenesis of peroxisome. At least three genes (HDNB1/UFD2, KIAA0591F/KIF1B-β, and PEX14) were differentially expressed at high levels in favorable and at low levels in unfavorable subsets of primary neuroblastoma. Since the 1p distal region is reported to be imprinted, those differentially expressed genes could be the new members of the candidate NBL suppressor, although RT-PCR-SSCP analysis has demonstrated infrequent mutation of the genes so far identified. Full-sequencing and gene prediction for the region of homozygous deletion would elucidate more detailed structure of this region and might lead to discovery of additional candidate genes.

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Acknowledgements

The authors thank Drs S Ichimiya, Y Nimura, and N Takada for helpful discussions, to Drs M Nagai, M Naka, T Iijima and S Saitoh for experimental support, to Ms A Morohashi, N Sugimitsu, E Kojima for technical assistance. We are grateful to Drs M Hamazaki and H Hiraiwa for providing the cell line and useful discussion and Dr M Oshimura for giving the hybrid cells. The authors also thank the hospitals and institutes collaborating with the Japanese Neuroblastoma Study Group for providing surgical specimens.

This work was supported in part by a grant-in-aid from the Ministry of Health and Welfare for a New Comprehensive 10-year Strategy for Cancer Control, Japan, by a grant-in-aid from the Ministry of Education, Science, and Culture of Japan, and by a grant from Uehara Memorial Foundation.

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  1. Miki Ohira and Hajime Kageyama: M Ohira and H Kageyama contributed to this work

Authors and Affiliations

  1. Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba, 260-8717, Japan

    Miki Ohira, Hajime Kageyama, Motohiro Mihara, Shigeyuki Furuta, Taiichi Machida, Tomotane Shishikura, Hajime Takayasu, Ashraful Islam, Yohko Nakamura, Masato Takahashi, Nobumoto Tomioka, Shigeru Sakiyama & Akira Nakagawara

  2. Department of Cancer Chemotherapy, Saitama Cancer Center Hospital, Saitama, 362-0806, Japan

    Yasuhiko Kaneko

  3. RIKEN Genomic Sciences Center, Sagamihara, 228-8555, Kanagawa, Japan

    Atsushi Toyoda & Masahira Hattori

  4. Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639, Japan

    Yoshiyuki Sakaki

  5. Cancer Genomics Division, National Cancer Center Research Institute, Chuoh-ku, Tokyo, 104-0045, Japan

    Misao Ohki

  6. Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, 980-8575, Japan

    Akira Horii

  7. RIKEN Gene Bank, Tsukuba, 305-0074, Ibaraki, Japan

    Eiichi Soeda

  8. Department of Molecular Cytogenetics, Division of Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan

    Johji Inazawa

  9. Biological Technology Laboratory, Helix Research Institute, Inc., Kisarazu, 292-0812, Chiba, Japan

    Naohiko Seki

  10. New Technology Development Department, Central Research Center, Hisamitsu Pharmaceutical Co., Inc., Tsukuba Research Laboratories, Tsukuba, 305-0856, Ibaraki, Japan

    Hidekazu Kuma & Iwao Nozawa

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  1. Miki Ohira
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Ohira, M., Kageyama, H., Mihara, M. et al. Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line. Oncogene 19, 4302–4307 (2000). https://doi.org/10.1038/sj.onc.1203786

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