A detailed transcriptional map of the chromosome 12p12 tumour suppressor locus

Abstract

Loss of heterozygosity of the short arm of chromosome 12 is a frequent event in a wide range of haematological malignancies and solid tumours. In previous studies, the shortest commonly deleted region was delimited to a 750-kb interval, defined by the markers D12S89 and D12S358, in pre-B acute lymphoblastic leukaemia patients, suggesting the presence of a tumour suppressor locus. Here we report the construction of a transcriptional map that integrates the data obtained by genomic sequence analysis, EST database search, comparative analysis and exon amplification. We identified seven putative transcriptional units as well as six pseudogenes. Four of these candidate genes were already known: ETV6, encoding an ets-like transcription factor, LRP6, a member of the LDL receptor gene family, BCL-G, a recently identified pro-apoptotic gene and MKP-7, encoding a new member of the dual-specificity phosphatase family. The products encoded by the three new genes identified in this study, LOH1CR12, LOH2CR12 and LOH3CR12, have no clear homology to known proteins. The gene predictions were all confirmed by expression analysis using RT–PCR and Northern blot. This transcriptional map is a crucial step toward the identification of the tumour suppressor gene at 12p12.