An integrated 5-Mb physical, genetic, and radiation hybrid map of a 1p36.1region implicated in neuroblastoma pathogenesis

Common genetic aberrations of neuroblastoma are deletions of the short arm of chromosome I (1p36) and MYCN amplification. Our deletion analysis of 25 tumor cell lines and 171 tumors strongly suggests that Ip harbors several t umor suppressor loci. Distinct loci are involved in MYCN single-copy versus MYCN-amplified neuroblastoma. Deletions in MYCN single-copy tumors have a shortest region of overlap (SRO) of 20 cM at 1p3.3. MYCN-amplified tumors h ave large deletions with an SRO of about 60 cM, from 1p36.1 to the telomere . This SRO is defined by D1S7(1p36.1), which was the most distal locus reta ined. Therefore, a suppressor gene associated with MYCN-amplified tumors pr obably maps within a few megabases distal of D1S7. In order to map this loc us, we further refined this SRO. We mapped the breakpoint of the MYCN-ampli fied neuroblastoma with the smallest Ip deletion between 56.6 and 57.2 cM f rom 1pter. Pulsed-field gel electrophoresis and radiation hybrid mapping we re used to construct a 5-Mb physical map of this region. The map includes t he region from 82.73 till 92.89 cR from 1pter. About half of it was isolate d in PI and PAC clones. The region harbors the genes FGR, SLC9A1, HMG17, EX TL1, AML2, RH, OP18, four ESTs, and a newly identified gene with a transcri pt size of approximately 7 Kb. Several of the mapped genes have a putative role in cell growth, differentiation, and morphogenesis. Genes Chromosomes Cancer 27:143-152, 2000. (C) 2000 Wiley-Liss, Inc.