Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Ann Hematol. 2012 Feb;91(2):193-201. doi: 10.1007/s00277-011-1289-x. Epub 2011 Jul 1.
SET-NUP214 rearrangement is a recently recognized recurrent chromosomal translocation mostly observed in T-ALL. In order to characterize this rare entity, we performed phenotypic and genetic characterization of SET-NUP214 rearrangement through an investigation of a series of 40 consecutive samples of adult T-ALL that was selected among 229 adult ALL cases during 4 years in a single institution. Four cases (10%) of SET-NUP214 translocation were identified in our study. In all cases, diagnosis of T-ALL was established according to the World Health Organization (WHO) classification, and clonal TCR rearrangements were found. The immunophenotypic markers were indicative of the precursor nature of T lymphoblasts, and they expressed one or both of the myeloid-associated antigens (CD13, CD33). Conventional cytogenetic analysis revealed complex chromosomal aberrations in all four SET-NUP214 rearranged cases and del(12)(p13)/ETV6 was frequently involved. Array-CGH demonstrated additional genomic imbalances in addition to deletion 9q34. The genomic breakpoint sequencing identified breakpoints at SET intron 7 and NUP214 intron 17, and random nucleotide addition was found in two cases at the site of rearrangement. Our independently derived data set from a single institution confirms previous findings of SET-NUP214 rearrangement, indicates the relatively high incidence of SET-NUP214 rearrangement in adult T-ALLs, and also demonstrates comprehensive clinical, phenotypic, and genetic characteristics of this entity. Also, our report on genomic breakpoints demonstrates the homogeneity in the localization of the genomic breakpoints at 9q34. Concurrent chromosomal aberrations identified in this study should provide further areas of interest in investigation of SET-NUP214-mediated leukemogenesis.
SET-NUP214 重排是一种最近被认识到的、常发生于 T-ALL 的染色体易位。为了对这种罕见的实体进行特征描述，我们对来自一个机构的 4 年内 229 例成人 ALL 中的 40 例连续成人 T-ALL 样本进行了 SET-NUP214 重排的表型和遗传学特征分析。在我们的研究中发现了 4 例（10%）SET-NUP214 易位。在所有病例中，根据世界卫生组织（WHO）分类诊断为 T-ALL，且发现克隆性 TCR 重排。免疫表型标志物提示 T 淋巴母细胞的前体细胞性质，并且它们表达一种或两种髓系相关抗原（CD13、CD33）。常规细胞遗传学分析显示所有 4 例 SET-NUP214 重排病例均存在复杂的染色体异常，并且经常涉及 del(12)(p13)/ETV6 缺失。阵列-CGH 除了 9q34 缺失之外还显示了额外的基因组不平衡。基因组断点测序确定了 SET 内含子 7 和 NUP214 内含子 17 的断点，并且在两个病例中发现了在重排部位的随机核苷酸添加。我们来自单个机构的独立数据集证实了 SET-NUP214 重排的先前发现，表明 SET-NUP214 重排在成人 T-ALL 中的相对高发率，并且还展示了该实体的全面临床、表型和遗传特征。此外，我们关于基因组断点的报告表明了在 9q34 处基因组断点定位的同质性。本研究中鉴定的并发染色体异常应在 SET-NUP214 介导的白血病发生的研究中提供进一步的关注领域。
