Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene (MSF) that map to a 17q25 region of loss in breast and ovarian tumors
Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene (MSF) that map to a 17q25 region of loss in breast and ovarian tumors
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DOI：
10.1006/geno.1999.6077
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发表时间：
2000-01-15
期刊：
影响因子：
4.4
通讯作者：
Petty, EM
中科院分区：
文献类型：
--
作者：
Kalikin, LM;Sims, HL;Petty, EM
我们以前在乳腺和卵巢肿瘤中定义了一个共同的17q25缺失区域，这表明至少有一个假定的肿瘤抑制基因的定位。使用来自该区间的基因组克隆来分离候选转录本。一个新的转录本与参与胞质分裂的GTPase基因的Septin家族有很强的同源性。该基因最近被鉴定为急性髓系白血病中的髓系/淋巴细胞性白血病(MLL)融合蛋白，命名为MSF(MLL Septin-like Fusion)。由于该基因可能在白血病发生和肿瘤发生中发挥作用，因此了解它的结构和正常表达是非常必要的。我们克隆了两个可供选择的人类转录本，并鉴定了MSF的第三个数据库变体。用三个新序列共有的探针进行的RNA表达研究表明，4.0和3.0kb的转录本在所有受测的成人和胎儿组织中都有差异表达。一个MSF变异体特有的探针跨越序列在所有组织中检测到4.0kb转录本的特异性表达。另一种不同MSF变体特有的探针仅在骨骼肌中检测到4.0kb的转录本。从新的交替转录本中预测了422和586个氨基酸的蛋白质，包括木糖异构酶1结构域和GTP酶结构域。共鉴定出9个常见外显子、3个选择性剪接外显子和6个多态性。(C)2000年学术出版社。
We previously defined a common region of 17q25 loss in breast and ovarian tumors, suggesting localization of at least one putative tumor suppressor gene. Genomic clones from the interval were used to isolate candidate transcripts. One novel transcript had strong homology to a septin family of GTPase genes involved in cytokinesis. This gene was recently identified as a myeloid/lymphoid leukemia (MLL) fusion protein partner in acute myeloid leukemia and was named MSF (MLL septin-like fusion). As this gene may play roles in both leukemogenesis and tumorigenesis, it is essential to understand its structure and normal expression. We cloned two human alternative transcripts and identified a third database variant of MSF. RNA expression studies with a probe common to the three novel sequences showed differential expression of 4.0- and 3.0-kb transcripts in all adult and fetal tissues tested. A probe spanning sequence unique to one MSF variant detected specific expression of the 4.0-kb transcript in all tissues. Another probe unique to a different MSF variant detected a 4.0-kb transcript only in skeletal muscle. Proteins of 422 and 586 amino acids were predicted from the novel alternate transcripts and included both a xylose isomerase 1 domain and a GTPase domain. Nine common exons, three alternatively spliced exons, and six polymorphisms were identified. (C) 2000 Academic Press.