Comprehensive Molecular Cytogenetic Analysis by Fluorescence In Situ Hybridization in Patients with Chronic Lymphocytic Leukemia
Julio A Diaz-Perez, Deirdre Amaro, Marie L Dell'Aquila, Huan-You Wang. UCSD Moores Cancer Center, La Jolla, CA
Background: Genomic aberrations can now be identified in the majority of patients with chronic lymphocytic leukemia (CLL) However; comprehensive molecular genetic analysis using the combination of multiple probes is limited. Here we report fluorescence in situ hybridization (FISH) results on 51 CLL cases by using 6 probes.
Design: Fifty one CLL patients with cytogenetic abnormalities at the diagnosis were retrieved from UCSD Cytogenetic Database. None of the patients had prior treatment. A total of 6 probes including ATM for 11q22.3, D12Z3 for chromosome 12 centromere, D13S319 for 13q14.3, LAMP1 for 13q34, p53 for chromosome 17p13.1, and CCND1/IGH for translocation (11;14) were used for each and every case of CLL. The bone marrow aspirate was used for FISH analysis in 51 out of 52 cases, the remaining one was performed on peripheral blood.
Results: Amongst 34 cases having conventional karyotype analysis, 52.9% (18/34) showed a normal karyotype. Molecular cytogenetic abnormalities observed, in the descending order, are as follows: deletion of 13q14.3 in 74.5% (38/51), trisomy 12 in 29.4% (15/51), deletion of ATM at 11q22.3 in 13.7% (7/51), deletion of p53 at 17p13 in 5.9% (3/51), and deletion of 13q43 in 2.0% (1/51) of cells, respectively. 2% of cases (1/51) have a gain of ATM gene. 25.4% (13/51) of cases harbor two abnormalities, and one case (2.0%) possesses three abnormalities. Amongst the cases having two abnormalities, 13q14.3 deletion with trisomy 12 is the most common followed by 13q14.3 deletion with deletion of ATM gene. Among 38 cases having deletion of 13q14.3, 28.9% (11/38) have both monoallelic and biallelic deletion of 13q14.3. None of the cases has CCND1/IGH.
Conclusions: Conventional karyotyping is not a reliable means in detecting the cytogenetic aberrancy in CLL, for in slightly greater than 50% of cases, karyotyping fails to detect any abnormalities. As previously reported, deletion of 13q14.3 is the most commonly observed abnormality in CLL, accounting for three quarters of the cases in our cohort of patients. Interestingly, close to one third of CLL patients who have deletion of 13q14.3 show two populations harboring monoallelic and biallelic deletions of q13.14.3, respectively.
Monday, March 19, 2012 1:00 PM
Poster Session II # 200, Monday Afternoon