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Cloning and Gene Mapping of the Chromosome 13q14 Region Deleted in Chronic Lymphocytic Leukemia
Authors:S Kalachikov  A Migliazza  E Cayanis  NS Fracchiolla  MF Bonaldo  L Lawton  P Jelenc  X Ye  X Qu  M Chien  R Hauptschein  G Gaidano  U Vitolo  G Saglio  L Resegotti  V Brodjansky  N Yankovsky  P Zhang  MB Soares  J Russo  IS Edelman  A Efstratiadis  R Dalla-Favera  SG Fischer
Institution:aColumbia Genome Center, Columbia University, New York, New York, 10032;bDepartment of Pathology, Columbia University, New York, New York, 10032;cDepartment of Psychiatry, Columbia University, New York, New York, 10032;hDepartment of Genetics and Development, Columbia University, New York, New York, 10032;dDipartimento di Scienze Mediche, Università di Torino, 28100, Novara, Italy;eLaboratorio di Medicina e Oncologia Molecolare, Dipartimento di Scienze Biomediche e Oncologia Umana, Ospedale San Luigi, Universita’ di Torino, 10043, Orbassano–Turin, Italy;fDivisione di Ematologia, A. O. San Giovanni Battista della Citta’ di Torino, 10126, Turin, Italy;gVavilov Institute of General Genetics, Moscow, 117809, Russia
Abstract:Frequent deletions and loss of heterozygosity in a segment of chromosome 13 (13q14) in cases of B-cell chronic lymphocytic leukemia (CLL) have suggested that this malignancy is caused by inactivation of an unknown tumor suppressor gene located in this region. Toward the identification of the putative CLL tumor suppressor, we have constructed a high-resolution physical map of YAC, PAC, and cosmid contigs covering 600 kb of the 13q14 genomic region. In addition to densely positioned genetic markers and STSs, this map was further annotated by localization of 32 transcribed sequences (ESTs) using a combination of exon trapping, direct cDNA selection, sample sequencing of cosmids and PACs, and homology searches. On the basis of these mapping data, allelic loss analyses at 13q14 using CLL tumor samples allowed narrowing of the genomic segment encompassing the putative CLL gene to <300 kb. Twenty-three ESTs located within this minimally deleted region are candidate exons for the CLL-associated tumor suppressor gene.
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