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Blood, 1 January 2004, Vol. 103, No. 1, pp. 283-290. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-01-0094. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0094v1 103/1/283    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Takagi, M. Articles by Mizutani, S. Search for Related Content PubMed PubMed Citation Articles by Takagi, M. Articles by Mizutani, S. Related Collections Cell Cycle Oncogenes and Tumor Suppressors Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Identification and characterization of polymorphic variations of the ataxia telangiectasia mutated (ATM) gene in childhood Hodgkin disease Masatoshi Takagi, Rika Tsuchida, Kaoru Oguchi, Teruko Shigeta, Shinichiro Nakada, Kimiko Shimizu, Misao Ohki, Domenico Delia, Luciana Chessa, Yoichi Taya, Makoto Nakanishi, Yukiko Tsunematsu, Fumio Bessho, Keiichi Isoyama, Yoshiki Hayashi, Kazuko Kudo, Jun Okamura, and Shuki Mizutani From the Department of Pediatrics and Developmental Biology, Postgraduate Medical School, Tokyo Medical and Dental University; the Molecular Oncology Division and the Radiobiology Division, National Cancer Center Research Institute; the Department of Hematology/Oncology, National Center for Child Health and Development; the Department of Pediatrics, Kyorin University; the Department of Pediatrics, Oume Municipal Hospital, Tokyo, Japan; the Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy; the Department of Experimental Medicine and Pathology, University "La Sapienza," Rome, Italy; the Department of Biochemistry, Nagoya City University Medical School, Nagoya, Japan; the Department of Pediatrics, Showa University of Medical School, Kanagawa, Japan; the Department of Pediatrics, Nagoya University, Nagoya, Japan; and the Section of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan. There are conflicting reports about the involvement of single nucleotide polymorphisms (SNPs) of the ataxia telangiectasia mutated (ATM) gene with cancer, and the consequences of these SNPs for ATM function remain unclear. We therefore sought to identify SNPs of the ATM gene in pediatric Hodgkin disease (HD) and to analyze ATM function in cells from patients with these SNPs. We have identified SNPs of the ATM gene in 5 of 14 children (S1455R, n = 1; H1380Y, n = 1; N1650S, n = 2; and I709I, n = 1). One patient had nonsense-associated altered splicing of the ATM gene. Lymphoblastoid cell lines expressing the S1455R and N1650S exhibited defective ATM-mediated p53 phosphorylation and Chk2 activation; cells expressing the H1380Y exhibited defective c-Abl activation after X-irradiation. Expression of the N1650S in ATM-null fibroblasts conferred only partial hyperradiosensitivity. Furthermore, the introduction of N1650S ATM into U2OS cells, which express wild-type ATM, showed reduced p53-Ser15 phosphorylation, suggesting a dominant-negative effect of the N1650S over the wild-type ATM protein. We conclude that the rare polymorphic variants of the ATM gene that we identified in children with HD encode functionally abnormal proteins, and we discuss the possible genetic risk factors for childhood HD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Stagni, M. G. di Bari, S. Cursi, I. Condo, M. T. Cencioni, R. Testi, Y. Lerenthal, E. Cundari, and D. Barila ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells Blood, January 15, 2008; 111(2): 829 - 837. [Abstract] [Full Text] [PDF] D. A. Hill, E. Gilbert, G. M. Dores, M. Gospodarowicz, F. E. van Leeuwen, E. Holowaty, B. Glimelius, M. Andersson, T. Wiklund, C. F. Lynch, et al. Breast cancer risk following radiotherapy for Hodgkin lymphoma: modification by other risk factors Blood, November 15, 2005; 106(10): 3358 - 3365. [Abstract] [Full Text] [PDF]

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