Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci
Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci
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DOI：
10.1038/sj.leu.2402884
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发表时间：
2003-04-01
期刊：
影响因子：
11.4
通讯作者：
Siebert, R
中科院分区：
文献类型：
--
作者：
Gesk, S;Martín-Subero, JI;Siebert, R
在T细胞受体（TCR）基因位点具有断点的染色体畸变在几种T细胞恶性肿瘤中复发。虽然间期细胞遗传学的重要性已被广泛显示在B细胞淋巴瘤，几乎没有任何分子细胞遗传学工具可用于T细胞疾病的复发性变化。因此，我们建立了基于荧光原位杂交（FISH）的TCRA/D（14 q11），TCRB（7 q34）和TCRG（7 p14）基因和TCL集群（14 q32）的分离分析。在正常对照以及43例经细胞遗传学证实为14 q11、7 q34 -35或7 p13 -21畸变的T细胞恶性肿瘤中验证了该测定。TCRA/D、TCRB和TCRG的断裂点可分别在32/33例染色体14 q11、3/6例染色体7 q34 -35和1/7例染色体7 p13 -21改变的T细胞肿瘤中通过这些测定来诊断。应用新的FISH检测一系列的24血管免疫母细胞和12皮肤T细胞淋巴瘤证实了缺乏在TCRA/D或TCRB基因座的断点的细胞遗传学证据。TCRA/D或TCRB断裂的同时检测是在一种荧光免疫表型分析方法中实现的，该方法进一步与在一种荧光免疫表型分析和间期细胞遗传学作为肿瘤研究的工具（Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasm）测定中检测T细胞特异性CD 3抗原相结合。这些新的FISH和FICTION检测为T细胞恶性肿瘤的诊断和生物学表征提供了灵敏、快速和准确的工具。
Chromosomal aberrations with breakpoints in T-cell receptor (TCR) gene loci are recurrent in several T-cell malignancies. Although the importance of interphase cytogenetics has been extensively shown in B-cell lymphomas, hardly any molecular cytogenetic tools are available for recurrent changes in T-cell disorders. Thus, we have established fluorescence in situ hybridization (FISH)-based break-apart assays for the TCRA/D (14q11), TCRB (7q34) and TCRG (7p14) genes and the TCL cluster (14q32). The assays were validated in normal controls as well as in 43 T-cell malignancies with cytogenetically proven 14q11, 7q34-35 or 7p13-21 aberrations. Breakpoints in TCRA/D, TCRB and TCRG could be diagnosed by these assays in 32/33 T-cell neoplasms with chromosome 14q11, 3/6 with 7q34-35 and 1/7 with 7p13-21 alterations, respectively. Application of the new FISH assays to a series of 24 angioimmunoblastic and 12 cutaneous T-cell lymphomas confirmed the cytogenetic evidence of lack of breakpoints in the TCRA/D or TCRB locus. Simultaneous detection of TCRA/D or TCRB breaks was achieved in a multicolor approach, which was further combined with detection of the T-cell-specific CD3 antigen in a multicolor FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasm) assay. These new FISH and FICTION assays provide sensitive, rapid and accurate tools for the diagnosis and biological characterization of T-cell malignancies.