Berggren P, Steineck G, Adolfsson J, Hansson J, Jansson O, Larsson P, Sandstedt B, Wijkström H, Hemminki K
Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden.
Br J Cancer. 2001 Jun 1;84(11):1505-11. doi: 10.1054/bjoc.2001.1823.
We have screened for mutations in exons 5-8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1-G2a) and 106 (56%) were highly malignant (G2b-G4 or > or = T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant.
我们在189例膀胱肿瘤患者中筛查了p53基因第5至8外显子的突变情况。82例(44%)肿瘤为低恶性(Ta,G1 - G2a),106例(56%)为高恶性(G2b - G4或≥T1)。仅1例低恶性膀胱肿瘤存在突变,在189例患者中,我们共发现26例(14%)存在p53突变。30%的样本在p53基因外源性(CA)n重复序列和p53基因内源性(AAAAT)n重复序列标记中的一个或两个出现杂合性缺失(LOH)。31个样本(21%)显示存在LOH但未发生突变,提示除突变外还有其他使p53失活的机制。在密码子280发现4个突变,在密码子285发现2个突变,这是之前报道的膀胱癌两个热点区域。该研究表明,在影响p53功能的遗传事件发生方面G2a和G2b肿瘤之间存在界限;中度分化(G2)的膀胱肿瘤可能在基因上具有异质性,这支持了不应将它们归为一类,而应例如分为低恶性或高恶性的建议。