Fine physical and transcript mapping of a 1.8 Mb region spanning the locus for childhood acute lymphoblastic leukemia on chromosome 12p12.3

• Published in: Gene Vol. 240; no. 2; pp. 297 - 305
• Main Authors: Aı̈ssani, B., Sinnett, D.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 29.11.1999
• Subjects: chromosome 12; Chromosome structure; CpG island; ETV6/TEL gene; KIP1 gene; Physical mapping; Pulse field gel electrophoresis; Satellite III; Tumor suppressor gene; YAC clones contig; Chromosome structure; FIGE, field inversion gel electrophoresis; Satellite III; AML1, acute myeloid leukemia; CpG island; p27/KIP1, cyclin-dependent kinase inhibitor; ClapS3, clathrin-adaptor small chain; YAC clones contig; CREBL2, Cre-binding protein-like 2; PRP, salivary proline-rich protein; Pulse field gel electrophoresis; ALL, acute lymphoblastic leukemia transcription factor 1; TEL/ETV6, ets-like transcription factor; PCR, polymerase chain reaction; Physical mapping; YAC variant 6, yeast artificial chromosome; Tumor suppressor gene
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/S0378-1119(99)00449-7

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 1.8 Mb 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 750 kb CpG-island rich region that includes the 240 kb 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.