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

Miki Ohira, Hajime Kageyama, Motohiro Mihara, Shigeyuki Furuta, Taiichi Machida, Tomotane Shishikura, Hajime Takayasu, Ashraful Islam, Yohko Nakamura, Masato Takahashi, Nobumoto Tomioka, Shigeru Sakiyama, Yasuhiko Kaneko, Atsushi Toyoda, Masahira Hattori, Yoshiyuki Sakaki, Misao Ohki, Akira Horii, Eiichi Soeda, Johji InazawaNaohiko Seki, Hidekazu Kuma, Iwao Nozawa, Akira Nakagawara

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 3 1/2 years (HDNB1/UFD2, KIAAO591F/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, KIAAO591F/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.

Original languageEnglish
Pages (from-to)4302-4307
Number of pages6
JournalOncogene
Volume19
Issue number37
Publication statusPublished - 2000 Aug 31
Externally publishedYes

Keywords

  • 1p36
  • Homozygous deletion
  • Neuroblastoma
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Ohira, M., Kageyama, H., Mihara, M., Furuta, S., Machida, T., Shishikura, T., Takayasu, H., Islam, A., Nakamura, Y., Takahashi, M., Tomioka, N., Sakiyama, S., Kaneko, Y., Toyoda, A., Hattori, M., Sakaki, Y., Ohki, M., Horii, A., Soeda, E., ... Nakagawara, A. (2000). Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line. Oncogene, 19(37), 4302-4307.