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DNA Polymerase ß Gene Mutation in Human Prostate Cancer¹

Department of Urology, Yokohama City University School of Medicine, 3–9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236, Japan

DNA polymerase ß 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 ß 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 ß 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 ß gene mutations, although they occurred at relatively low frequency, are involved in certain cases of human prostate carcinogenesis.

¹ This work was supported by Grants-in-aid 03454388, 05151013, and 05151032 from the Ministry of Education, Science and Culture of Japan.

² To whom requests for reprints should be addressed.

Received 12/13/93. Accepted 4/21/94.

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