13q14 Deletions Are Not Primary Events in B-Cell Chronic Lymphocytic Leukemia: A Study of 100 Patients Using Fluorescence

Fluorescence in situ hybridization with a chromosome 12-specific a-centromeric probe and a 13q14 yeast artificial chromosome probe was performed on interphase cells from 100 patients with B-cell chronic lymphocytic leukemia. Thirty-one patients exhibited a 13q14 deletion. No correlation was found between 13q14 deletions and clinical stage, sex, or morphology. Sixteen patients had trisomy 12, including 6 (of 12) with an atypical morphology. Trisomy 12 and 13q14 abnormalities were detected concomitantly in three patients only. The analysis of patients with deletions clearly showed that in five cases a significant number of cells retamed two signals with the yeast artificial chromosome probe, indicating a genetic heterogeneity among the leukemic population. Our data confirm that the 13q14 deletion is a frequent event, indicate that the concomitant occurrence of 13q14 deletion and trisomy 12 is rare but possible, and show that both abnormalities are secondary events in B-cell chronic lymphocytic leukemia. INTRODUCTION B-CLL3 is the most frequent leukemia in adults from Western countries. Chromosomal abnormalities are found in approximately 50% of the cases (1). The most common chromosomal abnormalities are trisomy 12 (2-4) and structural aberrations affecting 13q14 (4-7). In the other 50%, only normal metaphases are found, corresponding to the division of nonleukemic T cells (8, 9). Received 2/16/96; revised 6/18/96; accepted 7/15/96. I This work was supported by a grant from the Association pour la Recherche sur le Cancer. 2 To whom requests for reprints should be addressed, at Unite de Cytogenetique Hematologique, Laboratoire d’ H#{233}matologie, Institut de Biologie, Hotel Dieu, 9, Quai Moncousu, 44035 Nantes, C#{233}dex01, France. Phone: 33-40-08-40-34; Fax: 33-40-08-41-14. 3 The abbreviations used are: B-CLL, B-cell chronic lymphocytic leukemia; FISH, fluorescence in situ hybridization; Rb, retinoblastoma; YAC, yeast artificial chromosome; PL, prolymphocyte. Cytogenetic studies revealed trisomy 12 in 18 -30% of the cases with evaluable metaphases (4, 10), whereas FISH studies demonstrated it in 1 1-35% of the cases (1 1, 12). These differences may reflect different inclusion criteria or patient selection. Since trisomy 12 is a secondary event (13), the selection of patients with a more advanced disease stage would be expected to increase the frequency of this abnormality. Furthermore, this abnormality seems to be more frequent in patients with an atypical morphology (1 1) and could be associated with a poorer