HUMAN KRUPPEL-RELATED-3 (HKR3) - A CANDIDATE FOR THE 1P36 NEUROBLASTOMA TUMOR-SUPPRESSOR GENE

Human Kruppel-related 3 (HKR3) is a zinc finger gene that maps within chromosome subbands 1p36.2-.3, a region postulated to contain a tumour suppressor gene associated with advanced neuroblastomas. Genomic clon es of HKR3 were isolated from a P1 library and physically mapped to wi thin 40kb of D1S214 at 1p36.3. The gene is ubiquitously expressed in h uman tissues, but especially high levels are present in human fetal an d adult nervous tissues. Hemizygous deletion of HKR3 in a lymphoblasto id cell line derived from a neuroblastoma patient with a constitutiona l 1p36 interstitial deletion and in the neuroblastoma cell line SK-N-A S, which also has a small interstitial 1p36 deletion, has been observe d. Allelic loss at D1S214 in 15/15 informative primary neuroblastoma s pecimens with 1p36 deletions has also been observed. In a panel of 16 neuroblastoma cell lines, no gross genomic DNA rearrangements were not ed, the gene pas always expressed (albeit at variable levels) and ther e was no evidence for truncating mutations. Furthermore, there were no mutations detected in the zinc finger coding region in four neuroblas toma cell lines with Ip deletions analysed by direct sequence analysis . We conclude that HKR3 is a novel zinc finger gene that maps to a reg ion of the genome commonly rearranged or deleted in neuroblastoma and other human cancers. (C) 1997 Elsevier Science Ltd.