Miyao N, Tsai Y C, Lerner S P, Olumi A F, Spruck C H, Gonzalez-Zulueta M, Nichols P W, Skinner D G, Jones P A
Urologic Cancer Research Laboratory, Kenneth Norris Jr., Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles 90033.
Cancer Res. 1993 Sep 1;53(17):4066-70.
The tumors of 20 patients with multifocal primary transitional cell carcinoma of the bladder or lymph node metastases were examined for molecular genetic defects which we have previously found to be present in > 50% of invasive tumors. These included loss of heterozygosity (LOH) of chromosome 9, which occurs in superficial as well as invasive bladder tumors, and LOH of chromosome 17p and p53 mutations, which are commonly found only in invasive tumors. Analysis of multiple or recurrent primary tumors in 7 patients for these markers was generally consistent with recently published data that the tumors are monoclonal in origin and that p53 mutations occur as a late event in the generation of invasive bladder cancers. Comparison of the primary tumors and metastases to regional lymph nodes in 14 patients demonstrated a complete concordance between the molecular genetic defects present, showing that LOH of chromosomes 9 and 17p and p53 mutations occurred in the primary tumors before metastasis. Because of the importance of chromosome 9 in bladder cancer, we mapped the location of a putative tumor suppressor gene by restriction fragment length polymorphism analysis of 123 cases obtained in this and earlier studies. Most of the tumors showed LOH for more than one marker on chromosome 9. Results of mapping of 4 tumors with partial deletion of chromosome 9 suggests that the tumor suppressor gene is located between 9p12 and 9q34.1.
对20例患有多灶性原发性膀胱移行细胞癌或淋巴结转移瘤的患者的肿瘤进行了分子遗传学缺陷检测，我们此前发现这些缺陷存在于超过50%的浸润性肿瘤中。这些缺陷包括9号染色体杂合性缺失（LOH），其在浅表性以及浸润性膀胱肿瘤中均有发生，还有17号染色体短臂（17p）杂合性缺失和p53基因突变，后者通常仅在浸润性肿瘤中出现。对7例患者的多个或复发性原发性肿瘤进行这些标志物分析，结果总体上与最近发表的数据一致，即肿瘤起源于单克隆，且p53基因突变是浸润性膀胱癌发生过程中的晚期事件。对14例患者的原发性肿瘤和区域淋巴结转移瘤进行比较，结果显示存在的分子遗传学缺陷完全一致，表明9号和17号染色体短臂杂合性缺失以及p53基因突变在原发性肿瘤发生转移之前就已出现。由于9号染色体在膀胱癌中的重要性，我们通过对本研究及早期研究中获得的123例病例进行限制性片段长度多态性分析，绘制了一个假定的肿瘤抑制基因的位置。大多数肿瘤在9号染色体上显示出不止一个标志物的杂合性缺失。对4例9号染色体部分缺失的肿瘤进行定位分析的结果表明，肿瘤抑制基因位于9p12和9q34.1之间。
