1. ¹Division of Oncology, The Children's Hospital of Philadelphia, Department of Pediatrics, The University of Pennsylvania, Philadelphia, PA, USA
2. ²Division of Biostatistics and Data Management Core, Department of Pediatrics, The Children's Hospital of Philadelphia and Department of Pediatrics, The University of Pennsylvania, Philadelphia, PA, USA

Correspondence: Dr GM Brodeur, Division of Oncology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, ARC Rm. 902D, Philadelphia, PA 19104-4318, USA. E-mail: brodeur@email.chop.edu

³These authors contributed equally to this work.

Received 1 March 2007; Revised 17 April 2007; Accepted 25 May 2007; Published online 30 July 2007.

Abstract

Neuroblastomas are characterized by 1p deletions, suggesting that a tumor suppressor gene (TSG) resides in this region. We have mapped the smallest region of deletion (SRD) to a 2 Mb region of 1p36.31 using microsatellite and single nucleotide polymorphisms. We have identified 23 genes in this region, and we have analysed these genes for mutations and RNA expression patterns to identify candidate TSGs. We sequenced the coding exons of these genes in 30 neuroblastoma cell lines. Although rare mutations were found in 10 of the 23 genes, none showed a pattern of genetic change consistent with homozygous inactivation. We examined the expression of these 23 genes in 20 neuroblastoma cell lines, and most showed readily detectable expression, and no correlation with 1p deletion. However, 7 genes showed uniformly low expression in the lines, and 2 genes (CHD5, RNF207) had virtually absent expression, consistent with the expected pattern for a TSG. Our mutation and expression analysis in neuroblastoma cell lines, combined with expression analysis in normal tissues, putative function and prior implication in neuroblastoma pathogenesis, suggests that the most promising TSG deleted from the 1p36 SRD is CHD5, but TNFRSF25, CAMTA1 and AJAP1 are also viable candidates.