CLONING AND GENE-MAPPING OF THE CHROMOSOME 13Q14 REGION DELETED IN CHRONIC LYMPHOCYTIC-LEUKEMIA

Frequent deletions and loss of heterozygosity in a segment of chromoso me 13 (13q14) in cases of B-cell chronic lymphocytic leukemia (CLL) ha ve suggested that this malignancy is caused by inactivation of an unkn own tumor suppressor gene located in this region. Toward the identific ation of the putative (CLL tumor suppressor, we have constructed a hig h-resolution physical map of YAC, PAC, and cosmid contigs covering 600 kb of the 13q14 genomic region. In addition to densely positioned gen etic markers and STSs, this map was further annotated by localization of 32 transcribed sequences (ESTs) using a combination of exon trappin g, direct cDNA selection, sample sequencing of cosmids and PACs, and h omology searches. On the basis of these mapping data, allelic loss ana lyses at 13q14 using CLL tumor samples allowed narrowing of the genomi c 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. (C) 1997 Academic Press.