Homozygous deletion and expression of PTEN and DMBT1 in human primary neuroblastoma and cell lines

Neuroblastoma is the most common pediatric solid tumor. Although many allelic imbalances have been described, a bona fide tumor suppressor gene for this disease has not been found yet. In our study, we analyzed 2 genes, PTEN and DMBTI, mapping 10q23.31 and 10q25.3-26.1, respectively, which have been found frequently altered in other kinds of neoplasms. We screened both genes for homozygous deletions in 45 primary neuroblastic tumors and 12 neuroblastoma cell lines. Expression of these genes in cell lines was assessed by RT-PCR analysis. We could detect 2 of 41 (5%) primary tumors harboring PTEN homozygous deletions. Three of 41 (7%) primary tumors and 2 of 12 cell lines presented homozygous losses at the g14 STS on the DMBTI locus. All cell lines analyzed expressed PTEN, but lack of DMBTI mRNA expression was detected in 2 of them. We tried to see whether epigenetic mechanisms, such as aberrant promoter hypermethylation, had any role in DMBTI silencing. The 2 cell lines lacking DMBTI expression were treated with 5-aza-2'-deoxycytidine; DMBTI expression was restored in only one of them (MC-IXC). From our work, we can conclude that PTEN and DMBTI seem to contribute to the development of a small fraction of neuroblastomas, and that promoter hypermethylation might have a role in DMBTI gene silencing. (C) 2004 Wiley-Liss, Inc.