Wang D S, Rieger-Christ K, Latini J M, Moinzadeh A, Stoffel J, Pezza J A, Saini K, Libertino J A, Summerhayes I C
Department of Urology, Lahey Clinic, Burlington, MA, USA.
Int J Cancer. 2000 Nov 15;88(4):620-5. doi: 10.1002/1097-0215(20001115)88:4<620::aid-ijc16>3.0.co;2-z.
Loss of heterozygosity (LOH) on 10q is associated with late-stage events in urothelial neoplastic progression. The tumor suppressor gene PTEN, which is mutated or homozygously deleted in numerous cancers, maps to a region of 10q within the reported region of minimal loss in bladder tumors. In two recent studies alterations in the PTEN gene occur at a low frequency in bladder tumors displaying 10q LOH. We have screened 35 late-stage bladder tumors for mutations in PTEN and MXI1, both genes mapping to chromosome 10q. Using single-strand conformation polymorphism analysis, we identified 6 tumors harboring mutations in PTEN and 2 additional tumors displaying homozygous deletion at this locus. No MXI1 mutations were identified within the same tumor panel. Of 16 bladder tumor cell lines analyzed, 2 showed homozygous deletion of PTEN and 3 harbored point mutations resulting in an amino acid change. Two cell lines harbored missense mutations in MXI1. We report a significantly higher frequency of PTEN alterations in bladder carcinoma (23%) than was previously recorded, with no accompanying mutations in the MXI1 gene.
10号染色体长臂杂合性缺失（LOH）与尿路上皮肿瘤进展的晚期事件相关。肿瘤抑制基因PTEN在众多癌症中发生突变或纯合缺失，定位于膀胱肿瘤最小缺失报道区域内的10q区域。在最近的两项研究中，PTEN基因改变在显示10q LOH的膀胱肿瘤中发生频率较低。我们筛查了35例晚期膀胱肿瘤中的PTEN和MXI1基因的突变，这两个基因均定位于10号染色体长臂。通过单链构象多态性分析，我们鉴定出6例携带PTEN突变的肿瘤以及另外2例在该位点显示纯合缺失的肿瘤。在同一肿瘤组中未鉴定出MXI1突变。在分析的16株膀胱肿瘤细胞系中，2株显示PTEN纯合缺失，3株存在导致氨基酸改变的点突变。2株细胞系在MXI1中存在错义突变。我们报道膀胱癌中PTEN改变的频率（23%）显著高于先前记录，且MXI1基因无伴随突变。
