DETAILED MOLECULAR DELINEATION OF 13Q14.3 LOSS IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA

A region of chromosome 13q14.3, telomeric to the Retinoblastoma gene R B-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 th is locus. The contig clones have been used to order a number of marker s along the minimally deleted region and to localize a series of CpG i slands corresponding to possible candidate genes. A novel polymorphic dinucleotide repeat, 6E3.2, present in one of the ordered cosmid clone s has been isolated for use in deletion mapping studies of patient DNA . Leukemic samples from 229 CLL patients have been screened for loss o f heterozygosity using microsatellite markers and analyzed for hemizyg ous 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 l oss. The use of these probes has defined the commonly deleted area to less than 130 kb, centromeric to the locus D13S272. (C) 1998 by The Am erican Society of Hematology.