Interphase cytogenetics in chronic lymphocytic leukemia

The incidence of trisomy 12 and 13q12-q14 abnormalities in patients with chronic lymphocytic leukemia (CLL) was determined by conventional cytogenetics and interphase fluorescence in situ hybridization (FISH). In the analysis of 580 consecutive patients, trisomy 12 was detected by conventional cytogenetics in 39 cases (9%) and 117 cases (20%) by FISH. Trisomy 12 was shown to be associated with advanced clinical stage, atypical morphology, and higher proliferative activity. Combined immunophenotyping and FISH showed that trisomy 12 was present only in a proportion of the clonal B-cells. These data suggest that trisomy 12 is a secondary event associated with features of disease progression. Sequential FISH showed clonal progression of the trisomic clone over time. Three hundred patients also were investigated for 13q deletions using FISH analysis of the RB1 locus (13q14). Monoallelic RB1 deletion was seen in 104 (34%) of cases. One case had a homozygous deletion in 90% of the cells. Dual-color FISH detected the presence of trisomy 12 and RB1 in 17 (5%) cases. DNA probes for 13q12.3 (BRCA2) and 13q14 (RB1 and DBM locus) were used in 35 cases. Twenty-eight (80%) cases showed deletion of a 1Mb 13q12.3 encompassing the BRCA2 locus, whereas 22/35 (63%) were deleted at 13q14. Our data suggest that abnormalities of 13q are more frequent than trisomy 12 in CLL and provide evidence for the presence of a new candidate gene at 13q12.3 that may be involved in the pathogenesis of CLL.