von Lindern M, Fornerod M, Soekarman N, van Baal S, Jaegle M, Hagemeijer A, Bootsma D, Grosveld G
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Baillieres Clin Haematol. 1992 Oct;5(4):857-79. doi: 10.1016/s0950-3536(11)80049-1.
The t(6;9) that characterizes a specific subtype of ANLL fuses the 3' part of a gene located on chromosome 9q34, CAN, to the 5' part of a gene located on chromosome 6p23, DEK. On the 6p- chromosome, the resulting DEK-CAN fusion gene is transcribed into a leukaemia-specific 5.5 kb chimaeric mRNA that encodes a putative DEK-CAN fusion protein. No transcription could be detected from the reciprocal CAN-DEK fusion on chromosome 9q+. Analysis of 17 t(6;9) ANLL cases showed that the translocation breakpoints occur in a single intron of 7.5 kb in the CAN gene (ICB9) and in a single intron of 9 kb in the DEK gene (ICB6). As a result, the presence of a t(6;9) in blood or bone marrow cells can be faithfully diagnosed by Southern blotting. Moreover, the result of the translocation is an invariable DEK-CAN transcript, which can be sensitively monitored by RNA-PCR. Surprisingly, a SET-CAN fusion gene was found in leukaemic cells from a patient with AUL. Like CAN, SET is located on chromosome 9q34, which explains the apparently normal karyotype of the leukaemic cells. The occurrence of a SET-CAN fusion gene indicates that CAN may be the relevant oncogene involved in leukaemogenesis, and that activation of CAN can be effectuated through fusion of its 3' part to either DEK or SET. As yet, the function of CAN, DEK or SET is unknown. None of the proteins shows consistent homology to any known protein sequences. However, preliminary localization data and analysis of sequence motifs suggested that DEK-CAN may have a role in transcription regulation. CAN contains several dimerization domains and a repeated motif that can function as an ancillary DNA-binding domain. DEK and SET are non-related proteins, but they share a stretch of acidic amino acids, which is also present in the fusion proteins.
t(6;9)是急性非淋巴细胞白血病（ANLL）一种特定亚型的特征性标记，它将位于9号染色体q34的CAN基因的3'部分与位于6号染色体p23的DEK基因的5'部分融合。在6p-染色体上，产生的DEK-CAN融合基因转录成一种白血病特异性的5.5 kb嵌合mRNA，其编码一种假定的DEK-CAN融合蛋白。在9q+染色体上的反向CAN-DEK融合未检测到转录。对17例t(6;9) ANLL病例的分析表明，易位断点发生在CAN基因中一个7.5 kb的单一内含子（ICB9）和DEK基因中一个9 kb的单一内含子（ICB6）。因此，通过Southern印迹法可以准确诊断血液或骨髓细胞中是否存在t(6;9)。此外，易位的结果是一个恒定的DEK-CAN转录本，可通过RNA-PCR进行灵敏监测。令人惊讶的是，在一名急性未分化白血病（AUL）患者的白血病细胞中发现了SET-CAN融合基因。与CAN一样，SET位于9号染色体q34，这解释了白血病细胞明显正常的核型。SET-CAN融合基因的出现表明CAN可能是参与白血病发生的相关癌基因，并且CAN的激活可以通过其3'部分与DEK或SET融合来实现。目前，CAN、DEK或SET的功能尚不清楚。这些蛋白质均未显示与任何已知蛋白质序列有一致的同源性。然而，初步的定位数据和序列基序分析表明，DEK-CAN可能在转录调控中起作用。CAN含有几个二聚化结构域和一个可作为辅助DNA结合结构域的重复基序。DEK和SET是不相关的蛋白质，但它们共享一段酸性氨基酸序列，该序列也存在于融合蛋白中。
