MOLECULAR ANALYSIS OF THE REGION OF DISTAL 1P COMMONLY DELETED IN NEUROBLASTOMA

Cellular, cytogenetic, and molecular evidence indicates that chromosom e band 1p36 is often deleted in neuroblastoma cell lines and tumours, suggesting the presence of one or more tumour suppressor genes in this region. We used a multifaceted approach to analyse the commonly delet ed region. 28 distal 1p-specific polymorphic loci were used to detect loss of heterozygosity (LOH) in a panel of primary neuroblastoma tumou rs. Thirty-two of 122 tumours (26%) demonstrated LOH at three or more loci. In addition, a patient with a constitutional deletion of 1p36.2- .3 and two neuroblastoma cell lines with 1p36 abnormalities were chara cterised by FISH. When combined with the LOH data, a single consensus region of deletion was defined proximally by PLOD and distally by D1S8 0, a region spanning approximately five megabases. Several proposed ca ndidate tumour suppressor genes, including ID3, CDC2L1, DAN, PAX7, E2F 2, TNFR2 and TCEB3, map outside of this region; however, the transcrip tion factor HKR3 cannot be excluded. LOH for 1p is correlated with adv erse clinical and biological features and a poor prognosis, but 1p LOH is not an independent predictor of overall survival. To identify addi tional candidate genes, an integrated physical map of 1p35-36 is being constructed. The current map includes 445 polymerase chain reaction ( PCR)-formatted markers and 608 YACs. This map will help identify regio n-specific transcripts by direct selection and sequencing. (C) 1997 El sevier Science Ltd.