Garcia-Marco J A, Price C M, Catovsky D
Academic Department of Hematology and Cytogenetics, Royal Marsden Hospital, London, UK.
Cancer Genet Cytogenet. 1997 Mar;94(1):52-8. doi: 10.1016/s0165-4608(96)00304-4.
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.
采用传统细胞遗传学和间期荧光原位杂交（FISH）技术，测定慢性淋巴细胞白血病（CLL）患者中12号三体及13q12 - q14异常的发生率。在对580例连续患者的分析中，传统细胞遗传学检测到39例（9%）存在12号三体，FISH检测到117例（20%）存在12号三体。结果显示，12号三体与临床晚期、非典型形态及较高的增殖活性相关。联合免疫表型分析和FISH显示，12号三体仅存在于部分克隆性B细胞中。这些数据表明，12号三体是与疾病进展特征相关的继发性事件。连续FISH显示，随着时间推移，三体克隆存在克隆进展。还对300例患者进行了RB1基因座（13q14）的FISH分析，以检测13q缺失情况。104例（34%）出现单等位基因RB1缺失。1例在90%的细胞中存在纯合缺失。双色FISH在17例（5%）中检测到12号三体和RB1共存。对35例患者使用了13q12.3（BRCA2）和13q14（RB1和DBM基因座）的DNA探针。28例（80%）显示包含BRCA2基因座的1Mb 13q12.3缺失，而22/35例（63%）在13q14处缺失。我们的数据表明，CLL中13q异常比12号三体更常见，并为13q12.3处可能参与CLL发病机制的新候选基因的存在提供了证据。
