DNA fiber fluorescence in situ hybridization analysis of immunoglobulin class switching in B-cell neoplasia:: Aberrant CH gene rearrangements in follicle center-cell lymphoma
DNA fiber fluorescence in situ hybridization analysis of immunoglobulin class switching in B-cell neoplasia:: Aberrant CH gene rearrangements in follicle center-cell lymphoma
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DOI：
10.1182/blood.v92.8.2871.420k08_2871_2878
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发表时间：
1998-10-15
期刊：
影响因子：
20.3
通讯作者：
Kluin, PM
中科院分区：
文献类型：
--
作者：
Vaandrager, JW;Schuuring, E;Kluin, PM
免疫球蛋白类别转换通常涉及免疫球蛋白CH区的部分缺失。通过DNA纤维荧光原位杂交（FISH），用覆盖D-H、J（H）和C-H基因的探针条形码，可以在单个DNA分子上可视化整个C-H区域的构型。使用这种技术，我们研究了三种类型的B细胞瘤，套细胞淋巴瘤（MCL），滤泡性淋巴瘤（FL）和毛细胞白血病（HCL），代表B细胞，分别在pregermination中心，germination中心，和postgermination中心的发展阶段的类别转换。在MCL和FL中，分别用BCL-1和BCL-2基因座的探针同时检测t（11;14）和t（14;18）断点，可以区分生产性和非生产性等位基因。在10例MCL病例中没有检测到类别转换。在21例HCL中，所有非免疫球蛋白M（IgM）病例均具有与至少一个等位基因上表达的同种型一致的类别转换缺失。然而，在FL中，观察到一种特殊的C-H重排模式。在表达FL的IgM中，13例中有11例易位等位基因发生了转换，13例中有9例非易位等位基因在C mu-C delta基因下游表现出复杂的重排。这些下游重排可能反映了类转换机制的肿瘤特异性失调。所有7个免疫球蛋白G（IgG）表达FL显示两个等位基因的类转换。纤维FISH分析也显示了几个多态性。最常见的一个，存在于所有分析的等位基因的38%上，由3'簇中的额外C γ基因或假基因组成。(C)1998年，美国血液学会。
Immunoglobulin class switching usually involves deletion of part of the immunoglobulin CH region. By DNA fiber fluorescence in situ hybridization (FISH) with a barcode of probes covering the D-H, J(H), and C-H genes, the configuration of the entire C-H region can be visualized on single DNA molecules. Using this technique, we have studied class switching in three types of B-cell neoplasia, mantle-cell lymphoma (MCL), follicular lymphoma (FL) and hairy cell leukemia (HCL), representing B cells in, respectively, pregerminal center, germinal center, and postgerminal center stages of development. In MCL and FL, simultaneous detection of the t(11;14) and t(14;18) breakpoint with probes for the BCL-1 and BCL-2 loci, respectively, allowed differentiation between productive and nonproductive alleles. In none of 10 MCL cases was class switching detected. In 21 HCL, all nonimmunoglobulin M (IgM) cases had class-switch deletion consistent with the expressed isotype on at least one allele. In FL, however, a peculiar pattern of C-H rearrangement was observed. In IgM expressing FL, the translocated alleles had switched in 11 of 13 cases, and the nontranslocated allele showed complex rearrangements downstream from the C mu-C delta genes in 9 of 13 cases. These downstream rearrangements may reflect tumor-specific deregulation of the class-switch machinery. All seven immunoglobulin G (IgG) expressing FL showed class switching on both alleles. Fiber FISH analysis also showed several polymorphisms. The most frequent one, present on 38% of all analyzed alleles, consisted of an extra C gamma gene or pseudogene in the 3' cluster. (C) 1998 by The American Society of Hematology.