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

Loss of heterozygosity of the distal region of chromosome Ip where tumor su ppressor gene(s) might harbor is frequently observed in many human cancers including neuroblastoma (NBL) with MYCN amplification and poor prognosis. W e have identified for the first time a homozygously deleted region at the m arker D1S244 within the smallest region of overlap at 1p36.2-p36.3 in two N BL 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 w as made and partially sequenced (about 60%). The estimated length of the de leted region was 500 kb. We have, thus far, identified sis genes within the region which include three known genes (DFF45, PGD, and CORT) as well as t hree other genes which have been reported during processing our present pro ject for the last 31/2 years (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14). They include the genes related to apoptosis, glucose metabolism, ubiquitin -proteasome pathway, a neuronal microtubule-associated motor molecule and b iogenesis of peroxisome. At least three genes (HDNB1/UFD2, KIAA0591F/KIF1B- beta, and PEX14) were differentially expressed at high levels in favorable and at low levels in unfavorable subsets of primary neuroblastoma. Since th e Ip distal region is reported to be imprinted, those differentially expres sed genes could be the new members of the candidate NBL suppressor, althoug h RT-PCR-SSCP analysis has demonstrated infrequent mutation of the genes so far identified. Full-sequencing and gene prediction for the region of homo zygous deletion would elucidate more detailed structure of this region and might lead to discovery of additional candidate genes.