Molecular Cytogenetic Analysis of RB-1 Deletions in Chronic B-Cell Leukemias

Abstract

Deletions or translocations of 13q, most commonly involving band 13q14, belong to the most frequent structural chromosome abnormalities in B-cell chronic lymphocytic leukemia (B-CLL). In a combined metaphase and interphase cytogenetic study using conventional G-banding analysis and fluorescence in situ hybridization (ISH) we previously analysed the retinoblastoma susceptibility gene (RB-1) and its chromosomal locus 13q14 in 35 patients with chronic B-cell leukemias. We report here on the interphase cytogenetic analysis of 109 cases with chronic B-cell leukemias [B-CLL = 90; B-prolymphocytic leukemia (B-PLL) = 6, hairy cell leukemia (HCL) = 13]; a subset of 49 patients (B-CLL = 45; B-PLL = 4) was studied by conventional G-banding analysis. By G-banding, 5/45 (11%) patients with B-CLL had deletions or translocations affecting band 13q14; in contrast, ISH to interphase cells showed RB-1 deletion in 19/90 (21%) patients with B-CLL. No 13q14 abnormalities or RB-1 deletion were detected in patients with B-PLL and HCL. Our data confirm the high frequency of RB-1 deletions in B-CLL and further emphasize the possible pathogenetic role of this genomic region.

c‐MYC, RB‐1, TP53, and centromere 8 and 17 copy number in B‐cell non‐Hodgkin's lymphomas assessed by dual‐color fluorescence in situ hybridization

“…In contrast to earlier studies (14,15), our results indicate that RB-1 inactivation is not common in lymphomagenesis. Our results are in agreement with another FISH study that assessed RB-1 copy number in B-CLL (16). The important target for the 13q deletions is probably not RB-1 in 8 of 9 NHL cases with deletion of RB-1.…”

“…A FISH study of B-cell chronic lymphocytic leukemia (B-CLL) showed RB-1 deletion in 21% of the tumors. Only one case had homozygous deletion (16).…”

Trisomy 12 and structural abnormalities of 13q14 occurring in the same clone in chronic lymphocytic leukaemia

“…In our own study of > 400 cases, 15% had trisomy 12 and 16% had structural abnormalities of 13q14 . The incidence of both these abnormalities has consistently been found to be higher when fluorescence in situ hybridization (FISH) is performed on interphase cells using either an alpha centromeric probe specific for chromosome 12 or a probe for the retinoblastoma gene which is localized to 13q14 (Que et al, 1993;Dohner et al, 1994). This higher incidence reflects the fact that in cytogenetic studies of CLL either no metaphases may be obtained or the metaphases derive from normal T cells rather than the malignant B-cell clone.…”

dup(12)(q13–q22) and 13q14 Deletion in a Case of B-Cell Chronic Lymphocytic Leukemia

“…Molecular cytogenetic analysis has detected monoallelic deletions of the RB-1 (retinoblastoma) gene at the 13q14.2 locus in 30–40% of CLL patients [12, 13]. Subsequent studies showed that the D13S319 locus, between RB-1 and D13S25, had the highest frequency of deletions including homozygous deletions in 13% of CLL clones [14, 15], suggesting the presence of a new tumor suppressor gene involved in the pathogenesis of CLL.…”