Detailed Molecular Delineation of 13q14.3 Loss in B-Cell Chronic Lymphocytic Leukemia

Author:

Corcoran Martin M.1,Rasool Omid1,Liu Yie1,Iyengar Arati1,Grander Dan1,Ibbotson Rachel E.1,Merup Mats1,Wu Xiushan1,Brodyansky Vadim1,Gardiner Anne C.1,Juliusson Gunnar1,Chapman Robert M.1,Ivanova Ganka1,Tiller Mary1,Gahrton Gosta1,Yankovsky Nick1,Zabarovsky Eugene1,Oscier David G.1,Einhorn Stefan1

Affiliation:

1. From the Molecular Biology Laboratory, Royal Bournemouth General Hospital, Bournemouth, UK; Radiumhemmet, Karolinska Hospital, Stockholm Sweden; the Department of Medicine, Huddinge Hospital, Huddinge, Sweden; the Laboratory of Genome Analysis, Institute of General Genetics, Russian Academy of Science, Moscow, Russia; and the Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.

Abstract

Abstract A region of chromosome 13q14.3, telomeric to the Retinoblastoma gene RB-1 is frequently deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). A cosmid and P1-derived artificial chromosome (PAC) contig spanning over 600 kb has been constructed, which encompasses this locus. The contig clones have been used to order a number of markers along the minimally deleted region and to localize a series of CpG islands corresponding to possible candidate genes. A novel polymorphic dinucleotide repeat, 6E3.2, present in one of the ordered cosmid clones has been isolated for use in deletion mapping studies of patient DNA. Leukemic samples from 229 CLL patients have been screened for loss of heterozygosity using microsatellite markers and analyzed for hemizygous and homozygous deletions by Southern blot techniques using genomic probes selected from cosmids across the region. Hemizygous deletions were found in 31% of cases with an additional 10% showing homozygous loss. The use of these probes has defined the commonly deleted area to less than 130 kb, centromeric to the locus D13S272.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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