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

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

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

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

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

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

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

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

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

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

Correspondence to: Akira Nakagawara, Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chiba 260-8717, Japan

^aM Ohira and H Kageyama contributed to this work

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-, 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-, 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. Oncogene (2000) 19, 4302-4307

neuroblastoma; homozygous deletion; 1p36; tumor suppressor gene