FREQUENT HOMOZYGOUS DELETIONS OF THE D13S25 LOCUS IN CHROMOSOME REGION 13Q14 DEFINES THE LOCATION OF A GENE CRITICAL IN LEUKEMOGENESIS IN CHRONIC B-CELL LYMPHOCYTIC-LEUKEMIA

Cytogenetic studies of B-cell chronic lymphocytic leukaemia show struc tural abnormalities involving the 13q14 chromosome region as the only karyotypic change in a significant proportion of tumours. This observa tion suggests the location of a gene important in leukaemogenesis. A s eries of 68 BCLL tumours have been analysed for allele loss using a se ries of probes from 13q14. Using intragenic polymorphic markers from t he retinoblastoma predisposition gene LOH was observed in 25% of tumou rs including 3/6 showing cytogenetically obvious deletions of the 13q1 4 region and 3/6 showing translocations involving 13q14. However, thre e deletions with proximal breakpoints in 13q14 did not show allele los s, demonstrating that the breakpoint lay distal to RB1. Using the D13S 25 locus, which lies 1.6 cM distal to RB1, allele loss was seen in 90% of tumours with structural rearrangements of 13q14 and 75% of tumours with an apparently normal karyotype. 50% of these tumours showed homo zygous loss of D13S25, suggesting that a 'tumour suppressor gene' lies in this region. The more distal D13S31 locus, 1 cM distal to D13S25, was infrequently involved in allele loss demonstrating that the minimu m region of overlap for homozygous deletions is aproximately 1 Mbp aro und the D13S25 locus.