Dobashi Y, Shuin T, Tsuruga H, Uemura H, Torigoe S, Kubota Y
Department of Urology, Yokohama City University School of Medicine, Kanagawa, Japan.
Cancer Res. 1994 Jun 1;54(11):2827-9.
DNA polymerase beta is a nuclear protein essential to DNA repair in mammalian cells. A high frequency of mutations in this gene has been reported in colorectal cancers. To clarify the tumorigenesis steps of human prostate cancers in the molecular basis, we examined the entire coding region of the human DNA polymerase beta gene in human prostate cancer tissues using polymerase chain reaction, single-strand conformational polymorphism analysis of RNA, and sequencing analysis. Consequently, we detected DNA polymerase beta gene mutations in 2 of 12 cases (17%). The first case is an A to G transition at nucleotide 893, resulting in a substitution of the amino acid from tyrosine to cysteine. In the second case, we found an A to G transition at nucleotide 305, a T deletion at nucleotide 569, and an A insertion into the 6 repeats of A from nucleotide 612 to 617. This T deletion shifted the subsequent reading frame and resulted in the premature termination at codon 163 instead of 336. The two cases were advanced grade and stage. Present results suggest that polymerase beta gene mutations, although they occurred at relatively low frequency, are involved in certain cases of human prostate carcinogenesis.
DNA聚合酶β是哺乳动物细胞中DNA修复所必需的一种核蛋白。据报道，该基因在结直肠癌中具有高频率的突变。为了从分子基础上阐明人类前列腺癌的肿瘤发生步骤，我们使用聚合酶链反应、RNA的单链构象多态性分析和测序分析，检测了人类前列腺癌组织中人类DNA聚合酶β基因的整个编码区。结果，我们在12例中的2例（17%）中检测到DNA聚合酶β基因突变。第一例是第893位核苷酸由A向G的转变，导致氨基酸由酪氨酸替换为半胱氨酸。在第二例中，我们发现第305位核苷酸由A向G的转变、第569位核苷酸的T缺失以及从第612位至617位核苷酸处6个A重复序列中插入了一个A。这种T缺失使随后的阅读框发生移位，导致在第163位密码子而不是第336位密码子处提前终止。这两例均为高分级和高分期。目前的结果表明，聚合酶β基因突变虽然发生频率相对较低，但在某些人类前列腺癌发生病例中起作用。
