Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia
Autor: | R. Chapman, David Oscier, Gösta Gahrton, Vladimir I. Kashuba, Xiushan Wu, Rachel E. Ibbotson, N. K. Yankovsky, Andrew B. Poltaraus, Eugene R. Zabarovsky, Mary Tiller, Roman Müllenbach, Anna Baranova, Gunnar Juliusson, Anne Gardiner, Martin Corcoran, Stefan Einhorn, Finbarr E. Cotter, Omid Rasool, Mats Merup, Arati Iyengar, Anna Linda Hultström, Dan Grandér, Ganka Ivanova, Yie Liu |
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Rok vydání: | 1997 |
Předmět: |
Cancer Research
Transcription Genetic Tumor suppressor gene DNA Mutational Analysis Molecular Sequence Data Restriction Mapping Biology Polymerase Chain Reaction Homology (biology) Open Reading Frames Exon Restriction map Gene mapping Transferases Sequence Homology Nucleic Acid Genetics Humans Genes Tumor Suppressor Amino Acid Sequence Cloning Molecular Molecular Biology Gene Polymorphism Single-Stranded Conformational Base Sequence Chromosomes Human Pair 13 Contig Gene Expression Regulation Leukemic Tumor Suppressor Proteins Proteins DNA Neoplasm Cosmids Leukemia Lymphocytic Chronic B-Cell Molecular biology Neoplasm Proteins Cell Transformation Neoplastic Cosmid RNA Long Noncoding Gene Deletion |
Zdroj: | Scopus-Elsevier |
ISSN: | 1476-5594 0950-9232 |
DOI: | 10.1038/sj.onc.1201643 |
Popis: | Previous studies have indicated the presence of a putative tumor suppressor gene on chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have previously defined a minimally deleted region of 130 kb centromeric to the marker D13S272, and constructed a PAC and cosmid contig encompassing this area. In the present study we have made a detailed restriction and transcriptional map of the region of interest. Using these tools we have screened a panel of 206 primary CLL clones and three cell lines. In five CLL cases we found limited deletions defining the region of interest to an area of no more than 10 kb. Two adjacent genes, termed Leu1 and Leu2 (leukemia-associated gene 1 and 2), were mapped to the minimally deleted region, with several patients showing deletion borders within these genes. The Leu1 and Leu2 genes show little homology to previously published genes at the nucleotide and expected translated amino acid sequence level. Mutational analysis of the Leu1 and 2 genes in 170 CLL samples revealed no small intragenic mutations or point mutations. However, in all cases of 13q14 loss examined, the first exon of both genes, which are only 300 bp apart, were deleted. We conclude that the Leu1 and Leu2 genes are strong candidates as tumor suppressor gene(s) involved in B-CLL leukemogenesis. |
Databáze: | OpenAIRE |
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