Yong W H, Ueki K, Chou D, Reeves S A, von Deimling A, Gusella J F, Mohrenweiser H W, Buckler A J, Louis D N
Department of Pathology (Neuropathology), Massachusetts General Hospital, Charlestown 02129, USA.
Genomics. 1995 Sep 20;29(2):533-6. doi: 10.1006/geno.1995.9972.
Allelic loss studies have suggested that a glioma tumor suppressor gene resides in a 425-kb region of chromosome 19q, telomeric to D19S219 and centromeric to D19S112. Exon amplification of a cosmid contig spanning this region yielded four exons with high homology to a rat protein serine-threonine phosphatase from a cosmid approximately 100 kb telomeric to D19S219. Isolation of a near full-length cDNA from a human fetal brain cDNA library revealed a protein serine-threonine phosphatase with a tetratricopeptide motif, almost identical to human PPP5C (PP5) and highly homologous to rat PPT. Northern blotting demonstrated expression in most tissues, including brain. Primary and cultured gliomas were studied for genetic alterations in this gene using pulsed-field gel electrophoresis, routine Southern blots, and genomic DNA-and RNA-based single-strand conformation polymorphism analysis. Genomic alterations were were not detected in any of the gliomas, and all studied gliomas expressed the gene, suggesting that this phosphatase is not the putative chromosome 19q glioma tumor suppressor gene.
等位基因缺失研究表明，一种胶质瘤肿瘤抑制基因位于19号染色体q臂上一个425kb的区域，该区域在D19S219的端粒侧且在D19S112的着丝粒侧。对跨越该区域的黏粒重叠群进行外显子扩增，得到了四个与来自一个黏粒的大鼠蛋白丝氨酸 - 苏氨酸磷酸酶具有高度同源性的外显子，该黏粒位于D19S219端粒约100kb处。从人胎儿脑cDNA文库中分离出一个近全长cDNA，揭示了一种具有四肽重复基序的蛋白丝氨酸 - 苏氨酸磷酸酶，其与人类PPP5C（PP5）几乎相同且与大鼠PPT高度同源。Northern印迹分析表明该基因在包括脑在内的大多数组织中均有表达。使用脉冲场凝胶电泳、常规Southern印迹以及基于基因组DNA和RNA的单链构象多态性分析，对原发性和培养的胶质瘤进行了该基因的遗传改变研究。在任何胶质瘤中均未检测到基因组改变，并且所有研究的胶质瘤均表达该基因，这表明这种磷酸酶不是假定的19号染色体q臂胶质瘤肿瘤抑制基因。
