Kubota Y, Shuin T, Uemura H, Fujinami K, Miyamoto H, Torigoe S, Dobashi Y, Kitamura H, Iwasaki Y, Danenberg K
Department of Urology, Yokohama City University, School of Medicine, Japan.
Prostate. 1995 Jul;27(1):18-24. doi: 10.1002/pros.2990270105.
The genetic background underlying the growth and development of human prostatic cancer is not yet clear. Here we searched for possible mutations in the entire coding region of tumor suppressor gene p53 in primary human prostatic carcinomas, using polymerase chain reaction and single-strand conformational polymorphism analysis of RNA. We found p53 gene mutations in 4 of 21 cases (19%). DNA sequencing of the polymerase chain reaction products revealed missense point mutations that resulted in amino acid changes in exon 5 or 3 in three cases and single base deletions in exon 7 in two cases. One case contained both a missense point mutation and a single base deletion. Three of these four cases were pathologically diagnosed as poorly differentiated adenocarcinomas, and three of the four cases were clinically localized to stage C or D. None of seven noncancerous prostate tissues nor three well-differentiated adenocarcinoma tissues showed any mutations. The present results suggest that p53 gene mutation is involved in the late progression steps of human prostate carcinogenesis.
人类前列腺癌生长和发展背后的遗传背景尚不清楚。在此,我们利用聚合酶链反应和RNA的单链构象多态性分析,在原发性人类前列腺癌中寻找肿瘤抑制基因p53整个编码区域的可能突变。我们在21例中的4例(19%)发现了p53基因突变。对聚合酶链反应产物进行DNA测序显示,3例在第5外显子或第3外显子中出现导致氨基酸改变的错义点突变,2例在第7外显子中出现单碱基缺失。1例同时包含错义点突变和单碱基缺失。这4例中的3例经病理诊断为低分化腺癌,4例中的3例临床分期为C期或D期。7例非癌性前列腺组织和3例高分化腺癌组织均未显示任何突变。目前的结果表明,p53基因突变参与了人类前列腺癌发生的晚期进展步骤。