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  • Oncogenomics
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Allelic imbalance on chromosome 2q and alterations of the caspase 8 gene in neuroblastoma

Oncogene volume 20, pages 4424–4432 (2001)Cite this article

Abstract

We previously reported a high incidence of loss of heterozygosity (LOH) on chromosome 2q33 in neuroblastoma (NB), observed in various types of human cancers including lung cancer, head and neck cancer and follicular thyroid carcinoma. To better elucidate the role of chromosome 2q aberrations in NB, we examined common allelic imbalance (AI) regions on chromosome 2q in 82 NB patients using 10 polymorphic microsatellite markers. AI on 2q was detected in 26 (32%) of 82 NB cases. There was a distinct common AI region between the D2S115 and D2S307 markers on 2q33. The distance between these markers was about 2.0 cM. Recently, the caspase 8 and caspase 10 genes, both of which encode cystein protease, were mapped to chromosome 2q33. Since the common AI region on 2q33 includes the caspase 8 and caspase 10 genes, the alterations of these genes were examined further. Absent or reduced expression of caspase 8 and caspase 10 were found in 19 (70%) of 27 and two (7%) of 27 NB cell lines by reverse transcription-polymerase chain reaction, respectively. A missense mutation was detected at codon 96, GCT (Alanine) to GTT (Valine), of the caspase 8 gene in one of the NB cell lines lacking caspase 8 expression. Thirteen (68%) of 19 cell lines lacking caspase 8 expression displayed methylation of the CpG island of the caspase 8 gene, whereas only one (13%) of eight cell lines with caspase 8 expression showed caspase 8 methylation (P=0.031). Furthermore, there was a significant association between AI at 2q33 and loss of caspase 8 expression (P=0.026). These results indicated that there was a tumor suppressor gene in the common AI region on chromosome 2q33 involved in the pathogenesis of a subset of NB. It is possible that the caspase 8 gene is one of the candidate tumor suppressor genes for NB and inactivation of this gene plays an important role in the tumorigenesis of NB through mainly its methylation.

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Acknowledgements

We would like to thank Mrs S Sohma and H Soga for their excellent technical assistance. We would also like to express our appreciation to Drs AT Look, Harvard Medical University, and A Inoue, Toho University School of Medicine, for their generous gift of NB cell lines. This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for Research on Human Genome and Gene Therapy and Grants-in-Aid from the Ministry of Health and Welfare and from the Ministry of Education, Science and Culture of Japan. This work was also supported by NCI grant (NIH 2RD1 CA67938) to UK and by NIH grant 21765 to the Cancer Center of SJCRH and the generous support of the American Lebanese Syrian Associate Charities (ALSAC).

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Authors and Affiliations

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

    Junko Takita, Hong Wei Yang, Yu Yan Chen & Yasuhide Hayashi

  2. Division of Hematology/Oncology, Saitama Children's Medical Center, 2100 Magome, Iwatsuki, 339-0077, Saitama, Japan

    Ryoji Hanada & Keiko Yamamoto

  3. Department of Tumor Cell Biology, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, 38101, Tennessee, TN, USA

    Tal Teitz & Vincent Kidd

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  1. Junko Takita
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Correspondence to Yasuhide Hayashi.

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Takita, J., Yang, H., Chen, Y. et al. Allelic imbalance on chromosome 2q and alterations of the caspase 8 gene in neuroblastoma. Oncogene 20, 4424–4432 (2001). https://doi.org/10.1038/sj.onc.1204521

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