Center for Human Genetics, KU Leuven, Leuven, Belgium.
Leuk Lymphoma. 2012 Dec;53(12):2449-55. doi: 10.3109/10428194.2012.690098.
The genetic background of mature B-cell neoplasms with villous lymphocytes is poorly understood. We identified a novel breakpoint region at 14q32.13 that was rearranged together with IGH/14q32.33 in four cases of BRAF/V600E-negative leukemia/lymphoma with villous lymphocytes carrying either t(14;14)(q32.13;q32.33) (three patients) or del(14)(q32.13q32.33) (one patient). The 14q32.13 breakpoints were mapped by fluorescence in situ hybridization (FISH) in the region harboring the TCL1A/TCL1B/TCL6 genes, known to be affected by TCRA/D-mediated t(14;14)(q11;q32)/inv(14)(q11q32) occurring in T-cell leukemia/lymphoma. To identify the target of t(14;14)(q32.13; q32.33) and del(14)(q32.13q32.33), quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 25 candidate genes located centromerically and telomerically to the 14q32.13 breakpoint was performed. Any of the analyzed genes was commonly overexpressed in the presented cases. Of note, up-regulated transcription of TCL1A was observed in two cases. In summary, we provide evidence that IGH-mediated chromosomal aberrations affecting the 14q32.13/TCL1A-TCL6 region are recurrent in mature B-cell neoplasms with villous lymphocytes. Despite extensive qRT-PCR studies, molecular consequences of these novel aberrations remain elusive.
成熟 B 细胞肿瘤伴有绒毛状淋巴细胞的遗传背景了解甚少。我们鉴定了一个新的断裂点区域 14q32.13，该区域在 4 例 BRAF/V600E 阴性伴有绒毛状淋巴细胞的白血病/淋巴瘤中与 IGH/14q32.33 一起重排，这些肿瘤或携带 t(14;14)(q32.13;q32.33)（3 例）或 del(14)(q32.13q32.33)（1 例）。通过荧光原位杂交（FISH）在 TCL1A/TCL1B/TCL6 基因所在的区域定位 14q32.13 断裂点，该区域已知受 TCRD 介导的 t(14;14)(q11;q32)/inv(14)(q11q32)影响，该易位发生于 T 细胞白血病/淋巴瘤中。为了鉴定 t(14;14)(q32.13;q32.33)和 del(14)(q32.13q32.33)的靶点，对位于 14q32.13 断裂点着丝粒侧和端粒侧的 25 个候选基因进行了定量实时聚合酶链反应（qRT-PCR）分析。在呈现的病例中，任何分析的基因均普遍过表达。值得注意的是，在两个病例中观察到 TCL1A 的转录上调。总之，我们提供了证据，表明IGH 介导的染色体异常影响 14q32.13/TCL1A-TCL6 区域在成熟 B 细胞肿瘤伴有绒毛状淋巴细胞中是复发性的。尽管进行了广泛的 qRT-PCR 研究，但这些新异常的分子后果仍不清楚。
