Detailed molecular analysis of 1p36 in neuroblastoma

Background. Several lines of evidence establish that chromosome band 1p36 i s frequently deleted in neuroblastoma primary tumors and cell lines, sugges ting that a tumor suppressor gene within this region is involved in the dev elopment of this tumor. Procedure. We analyzed the status of 1p36 in primar y neuroblastomas and cell lines to define the region of consistent rearrang ement. Results. Loss of heterozygosity (LOH) studies of primary neuroblasto mss identified allelic loss in 135 of 503 tumors (27%), with the smallest r egion of overlap (SRO) defined distal to D1S214 (1p36.3). No homozygous del etions were detected at 120 loci mapping to 1p36.1-p36.3 in a panel of 46 n euroblastoma cell lines. A recently identified patient with neuroblastoma w as found to have a constitutional deletion within 1p36.2-p36.3, and this de letion, when combined with the LOH results, defined a smaller SRO of one me gabase within 1p36.3, We constructed a comprehensive integrated map of chro mosome 1 containing 11,000 markers and large-insert clones, a high-resoluti on radiation hybrid (RH) map of 1p36, and a P1-artificial chromosome (PAC) contig spanning the SRO, to further characterize the region of interest. Ov er 768 kb (75%) of the SRO has been sequenced to completion. Further analys is of distal lp identified 113 transcripts localizing to 1p36, 21 of which were mapped within the SRO. Conclusion. This analysis will identify suitabl e positional candidate transcripts for mutational screening and subsequent identification of the 1p36.3 neuroblastoma suppressor gene. Med. Pediatr. O ncol. 36: 37-41, 2001. (C) 2001 Wiley-Liss, Inc.