© 2005 Foundation for Promotion of Cancer Research
Cancer Genetics Report |
Genetic Alteration of Poly(ADP-ribose) Polymerase-1 in Human Germ Cell Tumors
1 Biochemistry Division, National Cancer Center Research Institute, Tokyo, 2 The 1st Department of Obstetrics and Gynecology, Toho University School of Medicine, Tokyo, 3 The Department of Neurosurgery, Dokkyo University School of Medicine, Iruma-gun, Saitama and 4 The Department of Neurosurgery, Saitama Medical University, Shimotsuga-gun, Tochigi, Japan
For reprints and all correspondence: Dr Mitsuko Masutani, Biochemistry Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. E-mail: mmasutan{at}gan2.res.ncc.go.jp
Received October 8, 2004; accepted December 11, 2004
Accumulated evidence suggests that poly(ADP-ribose) polymerase-1 (PARP-1) is involved in DNA repair, cell-death induction, differentiation and tumorigenesis. Parp-1 deficiency also induces trophoblast differentiation from mouse embryonic stem cells during teratocarcinoma-like tumor formation. To understand the relationship of PARP-1 dysfunction and development of germ cell tumors, we conducted a genetic analysis of the PARP-1 gene in human germ cell tumors. Sixteen surgical specimens of germ cell tumors that developed in the brain and testes were used. Two known single nucleotide polymorphisms (SNPs) (Val762Ala and Lys940Arg), which are listed in the SNP database of the NCBI (National Center for Biotechnology Information), were detected. In both cases, cSNPs encoded amino acids located within peptide stretches in the catalytic domain, which are highly conserved among various animal species. Furthermore, another novel sequence alteration, a base change of ATG to ACG, was identified in a tumor specimen, which would result in the amino acid substitution, Met129Thr. This base change was observed in one allele of both tumor and normal tissues, suggesting that it is either a rare SNP or a germline mutation of the PARP-1 gene. Notably, the amino acid Met129 is located within the second zinc finger domain, which is essential for DNA binding and is conserved among animal species. One SNP in intron 2 and one in the upstream 5'-UTR (untranslated region) were also detected.
Key Words: brain • germ cell tumor • mutations • poly(ADP-ribose) polymerase-1 • SNP
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