Fine physical and transcript mapping of a 1.8 Mb region spanning the locus for childhood acute lymphoblastic leukemia on chromosome 12p12. 3.
Rearrangements of the short arm of chromosome 12 are frequently observed in hematological disorders. Previous studies of loss of heterozygosity identified a small genetic interval on chromosome 12p12.3 that is frequently deleted in childhood acute lymphoblastic leukemia (ALL). Two genes, ETV6/TEL and p27/KIP1, are located in this interval. Evidence has accumulated that an as-yet unidentified tumor suppressor gene is closely linked to these. To facilitate the identification of candidate genes, a long-range high-resolution restriction map of the ALL locus was constructed using a contig of YAC clones. Several marker loci, including 11 STS, three newly developed YAC end-based STS, six EST, and seven genes were unambiguously positioned in the new map. The map covers 1.8Mb and extends from the distal salivary proline-rich protein gene cluster to the proximal p27/KIP1 gene. The data confirmed the order tel-D12S358-p27/KIP1-cen and excluded p27/KIP1 as a candidate tumor suppressor gene. The critical region delimited by D12S89 and D12S358 is a 750kb CpG-island rich region that includes the 240kb TEL/ETV6 gene as well as CLAPS3 (clathrin-adaptor small chain 3). The new map provides a molecular framework for the identification of novel genes and transcriptional units in the ALL interval.
Aïssani
B
B
Division of Hematology-Oncology, Charles-Bruneau Cancer Center, Research Center, Sainte-Justine Hospital, 3175 Côte Ste-Catherine, Montreal, Canada.
Sinnett
D
D
D033963:Adaptor Protein Complex 3; D034002:Adaptor Protein Complex sigma Subunits; D000818:Animals; D018797:Cell Cycle Proteins; D002648:Child; D018244:Chromosomes, Artificial, Yeast; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D020451:Contig Mapping; D006224:Cricetinae; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020224:Expressed Sequence Tags; D006801:Humans; D006822:Hybrid Cells; D018895:Microsatellite Repeats; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010455:Peptides / Q000235:genetics; D020161:Physical Chromosome Mapping; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D055232:Proline-Rich Protein Domains; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D016324:Sequence Tagged Sites; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins; D000097764:ETS Translocation Variant 6 Protein
D033963:Adaptor Protein Complex 3; D034002:Adaptor Protein Complex sigma Subunits; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C115637:AP3S1 protein, human