Comprehensive genetic characterization of CLL:: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping
Comprehensive genetic characterization of CLL:: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and immunophenotyping
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DOI：
10.1038/sj.leu.2404935
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发表时间：
2007-12-01
期刊：
影响因子：
11.4
通讯作者：
Haferlach, T.
中科院分区：
文献类型：
--
作者：
Haferlach, C.;Dicker, F.;Haferlach, T.
由于CLL细胞在体外的低增殖活性，来自染色体显带分析（CBA）的γ In CLL数据一直是稀缺的。我们使用免疫刺激性CpG寡核苷酸DSP 30和IL-2改进了培养技术。共506例CLL样本进行CBA和间期FISH分析，使用探针检测12三体、IgH重排和6 q21、11q22.3（ATM）、13 q14（D13 S25和D13 S319）和17 p13（TP 53）缺失。共500/506例（98.8%）成功刺激中期生成，并接受本研究。CBA检出异常415例（83.0%），FISH检出异常392例（78.4%）。CBA检测到832个异常，FISH仅检测到502个异常。因此，CBA提供了除FISH之外的重要信息。(1)CLL的主要特征是基因组不平衡和相互易位是罕见的。(2)鉴定出具有复杂异常核型的亚组（16.4%），其与未突变的IgV（H）状态和CD 38表达相关（分别为P=0.034和0.02）。(3)额外的异常是可检测的，提供了对不同CLL亚类的新的生物学见解，揭示了迄今为止仅基于FISH数据假设的更异质的细胞遗传学异常模式。因此，前瞻性临床试验应评估新获得的CBA数据的预后影响。
yIn CLL data from chromosome banding analysis (CBA) have been scarce due to the low proliferative activity of CLL cells in vitro. We improved the cultivation technique using an immunostimulatory CpG-oligonucleotide DSP30 and IL-2. A total of 506 CLL samples were analysed with CBA and interphase FISH using probes for the detection of trisomy 12, IgH rearrangements and deletions of 6q21, 11q22.3 (ATM), 13q14 (D13S25 and D13S319) and 17p13 (TP53). A total of 500 of 506 ( 98.8%) cases were successfully stimulated for metaphase generation and are subject to this study. Aberrations were detected in 415 of 500 (83.0%) cases by CBA and in 392 of 500 (78.4%) cases by FISH. CBA detected 832 abnormalities and FISH only 502. Therefore, CBA offers important information in addition to FISH. (1) CLL is characterized mainly by genomic imbalances and reciprocal translocations are rare. (2) A subgroup with complex aberrant karyotype (16.4%) is identified which is associated with an unmutated IgV(H) status and CD38 expression (P=0.034 and 0.02, respectively). (3) Additional abnormalities are detectable providing new biological insights into different CLL subclasses revealing a much more heterogeneous pattern of cytogenetic abnormalities as assumed so far based on FISH data only. Therefore, prospective clinical trials should evaluate the prognostic impact of newly available CBA data.