Mechanisms of therapy-related carcinogenesis (original) (raw)

• Rowland, J. et al. Cancer survivorship — United States, 1971–2001. MMWR Morb. Mortal. Wkly Rep. 53, 526–529 (2004).
  Google Scholar
• van Leeuwen, F. & Travis, L. B. in Cancer: Principles and Practice of Oncology 2575–2602 (Lippincott Williams and Wilkin, Philadelphia, 2005).
  Google Scholar
• Warren, S. & Gates, O. Multiple primary malignant tumors: a survey of the literature and statistical study. Am. J. Cancer 16, 1358–1414 (1932).
  Google Scholar
• SEER Cancer Statistics Review, 1975–2002 (eds Ries, L. et al.) (National Cancer Institute, Bethesda, Maryland, 2003). http://seer.cancer.gov/csr/1975_2002/
• Travis, L. B. Therapy-associated solid tumors. Acta Oncol. 41, 323–333 (2002).
  PubMed Google Scholar
• Kinlen, L. J. in Cancer Epidemiology and Prevention (ed. Schottenfeld, D.) 532–545 (Oxford University Press, New York, 1996).
  Google Scholar
• Allan, J. M. & Rabkin, C. S. Genetic susceptibility to iatrogenic malignancy. Pharmacogenomics 6, 615–628 (2005).
  CAS PubMed Google Scholar
• Hoppe, R. T. Hodgkin's disease: complications of therapy and excess mortality. Ann. Oncol. 8 (suppl.), 115–118 (1997).
  PubMed Google Scholar
• Aleman, B. M. et al. Long-term cause-specific mortality of patients treated for Hodgkin's disease. J Clin. Oncol. 21, 3431–3439 (2003).
  PubMed Google Scholar
• Dores, G. M. et al. Long-term cause-specific mortality among 41,146 one-year survivors of Hodgkin lymphoma (HL). J. Clin. Oncol. 23 (suppl.), 6511 (2005).
  Google Scholar
• Boice, J. D., Land, C. E. & Preston, D. L. in Cancer Epidemiology and Prevention (ed. Schottenfeld, D.) 319–354 (Oxford University Press, New York, 1996).
  Google Scholar
• Behrens, C. et al. Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease. Cancer Epidemiol. Biomarkers Prev. 9, 1027–1035 (2000).
  CAS PubMed Google Scholar
• Gafanovich, A. et al. Microsatellite instability and p53 mutations in pediatric secondary malignant neoplasms. Cancer 85, 504–510 (1999).
  CAS PubMed Google Scholar
• Gilbert, E. S. et al. Lung cancer after treatment for Hodgkin's disease: focus on radiation effects. Radiat. Res. 159, 161–173 (2003). Demonstrated an additive effect for radiotherapy and chemotherapy on the risk of developing lung cancer after Hodgkin disease, but a multiplicative effect for radiation and smoking, and for chemotherapy and smoking.
  CAS PubMed Google Scholar
• Richardson, C. & Jasin, M. Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 405, 697–700 (2000).
  CAS PubMed Google Scholar
• Lovett, B. D. et al. Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation. Proc. Natl Acad. Sci. USA 98, 9802–9807 (2001).
  CAS PubMed Google Scholar
• Atlas, M. et al. Cloning and sequence analysis of four t(9;11) therapy-related leukemia breakpoints. Leukemia 12, 1895–1902 (1998).
  CAS PubMed Google Scholar
• Whitmarsh, R. J. et al. Reciprocal DNA topoisomerase II cleavage events at 5′-TATTA-3′ sequences in MLL and AF-9 create homologous single-stranded overhangs that anneal to form der(11) and der(9) genomic breakpoint junctions in treatment-related AML without further processing. Oncogene 22, 8448–8459 (2003).
  CAS PubMed Google Scholar
• Zhang, Y. et al. Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia. Proc. Natl Acad. Sci. USA 99, 3070–3075 (2002).
  CAS PubMed Google Scholar
• Mistry, A. R. et al. DNA topoisomerase II in therapy-related acute promyelocytic leukemia. N. Engl. J. Med. 352, 1529–1538 (2005).
  CAS PubMed Google Scholar
• Hess, J. L., Yu, B. D., Li, B., Hanson, R. & Korsmeyer, S. J. Defects in yolk sac hematopoiesis in _Mll_-null embryos. Blood 90, 1799–1806 (1997).
  CAS PubMed Google Scholar
• Fidanza, V. et al. Double knockout of the ALL-1 gene blocks hematopoietic differentiation in vitro. Cancer Res. 56, 1179–1183 (1996).
  CAS PubMed Google Scholar
• Pedersen-Bjergaard, J. & Rowley, J. D. The balanced and the unbalanced chromosome aberrations of acute myeloid leukemia may develop in different ways and may contribute differently to malignant transformation. Blood 83, 2780–2786 (1994).
  CAS PubMed Google Scholar
• Felix, C. A. Secondary leukemias induced by topoisomerase-targeted drugs. Biochim. Biophys. Acta 1400, 233–255 (1998).
  CAS PubMed Google Scholar
• Lovett, B. D. et al. Etoposide metabolites enhance DNA topoisomerase II cleavage near leukemia-associated MLL translocation breakpoints. Biochemistry (Mosc). 40, 1159–1170 (2001).
  CAS Google Scholar
• Aplan, P. D., Chervinsky, D. S., Stanulla, M. & Burhans, W. C. Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors. Blood 87, 2649–2658 (1996).
  CAS PubMed Google Scholar
• Domer, P. H. et al. Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and identification of topoisomerase II consensus-binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11). Leukemia 9, 1305–1312 (1995).
  CAS PubMed Google Scholar
• Broeker, P. L. et al. Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites. Blood 87, 1912–1922 (1996).
  CAS PubMed Google Scholar
• Raffini, L. J. et al. Panhandle and reverse-panhandle PCR enable cloning of der(11) and der(other) genomic breakpoint junctions of MLL translocations and identify complex translocation of MLL, AF-4, and CDK6. Proc. Natl Acad. Sci. USA 99, 4568–4573 (2002).
  CAS PubMed Google Scholar
• Strissel, P. L., Strick, R., Rowley, J. D. & Zeleznik, L. An in vivo topoisomerase II cleavage site and a DNase I hypersensitive site colocalize near exon 9 in the MLL breakpoint cluster region. Blood 92, 3793–3803 (1998).
  CAS PubMed Google Scholar
• Libura, J., Slater, D. J., Felix, C. A. & Richardson, C. Therapy-related acute myeloid leukemia-like MLL rearrangements are induced by etoposide in primary human CD34+ cells and remain stable after clonal expansion. Blood 105, 2124–2131 (2005). Demonstrated the direct induction of MLL gene rearrangements in CD34-positive haematopoietic progenitor cells by exposure to etoposide.
  CAS PubMed Google Scholar
• Ayton, P. M. & Cleary, M. L. Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 20, 5695–5707 (2001).
  CAS PubMed Google Scholar
• Wang, J. et al. Conditional MLL–CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J. 24, 368–381 (2005). Developed a mouse model of Mll - translocated, therapy-related leukaemia, and demonstrated the transforming potential of the chimeric oncoprotein.
  PubMed PubMed Central Google Scholar
• Sobulo, O. M. et al. MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). Proc. Natl Acad. Sci. USA 94, 8732–8737 (1997).
  CAS PubMed Google Scholar
• So, C. W. et al. MLL–GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell 3, 161–171 (2003).
  CAS PubMed Google Scholar
• Forster, A. et al. Engineering de novo reciprocal chromosomal translocations associated with Mll to replicate primary events of human cancer. Cancer Cell 3, 449–458 (2003).
  CAS PubMed Google Scholar
• Corral, J. et al. An Mll_–_AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell 85, 853–861 (1996).
  CAS PubMed Google Scholar
• Dobson, C. L. et al. The mll_–_AF9 gene fusion in mice controls myeloproliferation and specifies acute myeloid leukaemogenesis. EMBO J. 18, 3564–3574 (1999).
  CAS PubMed PubMed Central Google Scholar
• Yuan, Y. et al. AML1–ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc. Natl Acad. Sci. USA 98, 10398–10403 (2001).
  CAS PubMed Google Scholar
• Ono, R. et al. Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple-lineage leukemogenesis. J. Clin. Invest. 115, 919–929 (2005). Elegant study showing that FLT3 mutation secondary to an MLL fusion was sufficient to generate myeloid leukaemia in a mouse model.
  CAS PubMed PubMed Central Google Scholar
• World Heath Organisation. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 76: Some Antiviral and Antineoplastic Drugs, and Other Pharmaceutical Agents (International Agency for Research on Cancer, 2000).
• Megonigal, M. D. et al. Detection of leukemia-associated MLL_–_GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors. Proc. Natl Acad. Sci. USA 97, 2814–2819 (2000).
  CAS PubMed Google Scholar
• Stanulla, M., Wang, J., Chervinsky, D. S., Thandla, S. & Aplan, P. D. DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis. Mol. Cell Biol. 17, 4070–4079 (1997).
  CAS PubMed PubMed Central Google Scholar
• Betti, C. J., Villalobos, M. J., Diaz, M. O. & Vaughan, A. T. Apoptotic triggers initiate translocations within the MLL gene involving the nonhomologous end joining repair system. Cancer Res. 61, 4550–4555 (2001).
  CAS PubMed Google Scholar
• Betti, C. J., Villalobos, M. J., Diaz, M. O. & Vaughan, A. T. Apoptotic stimuli initiate MLL_–_AF9 translocations that are transcribed in cells capable of division. Cancer Res. 63, 1377–1381 (2003).
  CAS PubMed Google Scholar
• Sim, S. P. & Liu, L. F. Nucleolytic cleavage of the mixed lineage leukemia breakpoint cluster region during apoptosis. J Biol. Chem. 276, 31590–31595 (2001).
  CAS PubMed Google Scholar
• Langer, T. et al. Analysis of t(9;11) chromosomal breakpoint sequences in childhood acute leukemia: almost identical MLL breakpoints in therapy-related AML after treatment without etoposides. Genes Chromosomes Cancer 36, 393–401 (2003).
  CAS PubMed Google Scholar
• Eguchi-Ishimae, M. et al. Breakage and fusion of the TEL (ETV6) gene in immature B lymphocytes induced by apoptogenic signals. Blood 97, 737–743 (2001).
  CAS PubMed Google Scholar
• Loeb, L. A. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 51, 3075–3079 (1991).
  CAS PubMed Google Scholar
• Loeb, L. A., Springgate, C. F. & Battula, N. Errors in DNA replication as a basis of malignant changes. Cancer Res. 34, 2311–2321 (1974).
  CAS PubMed Google Scholar
• Ben Yehuda, D. et al. Microsatellite instability and p53 mutations in therapy-related leukemia suggest mutator phenotype. Blood 88, 4296–4303 (1996).
  CAS PubMed Google Scholar
• Zhu, Y. M., Das-Gupta, E. P. & Russell, N. H. Microsatellite instability and p53 mutations are associated with abnormal expression of the MSH2 gene in adult acute leukemia. Blood 94, 733–740 (1999).
  CAS PubMed Google Scholar
• Worrillow, L. J. et al. An intron splice acceptor polymorphism in hMSH2 and risk of leukemia after treatment with chemotherapeutic alkylating agents. Clin. Cancer Res. 9, 3012–3020 (2003).
  CAS PubMed Google Scholar
• Offman, J. et al. Defective DNA mismatch repair in acute myeloid leukemia/myelodysplastic syndrome after organ transplantation. Blood 104, 822–828 (2004). Demonstrated a substantially increased risk of developing leukaemia in patients who were given azathioprine for solid organ transplant, and that the resulting leukaemias are DNA-MMR-defective.
  CAS PubMed Google Scholar
• Horiike, S. et al. Distinct genetic involvement of the TP53 gene in therapy-related leukemia and myelodysplasia with chromosomal losses of Nos 5 and/or 7 and its possible relationship to replication error phenotype. Leukemia 13, 1235–1242 (1999).
  CAS PubMed Google Scholar
• Sheikhha, M. H., Tobal, K. & Liu Yin, J. A. High level of microsatellite instability but not hypermethylation of mismatch repair genes in therapy-related and secondary acute myeloid leukaemia and myelodysplastic syndrome. Br. J. Haematol. 117, 359–365 (2002).
  CAS PubMed Google Scholar
• Reese, J. S., Liu, L. & Gerson, S. L. Repopulating defect of mismatch repair-deficient hematopoietic stem cells. Blood 102, 1626–1633 (2003).
  CAS PubMed Google Scholar
• Margison, G. P. & Santibanez-Koref, M. F. O6-alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy. Bioessays 24, 255–266 (2002).
  CAS PubMed Google Scholar
• Kat, A. et al. An alkylation-tolerant, mutator human cell line is deficient in strand-specific mismatch repair. Proc. Natl Acad. Sci. USA 90, 6424–6428 (1993).
  CAS PubMed Google Scholar
• Karran, P. & Bignami, M. DNA damage tolerance, mismatch repair and genome instability. Bioessays 16, 833–839 (1994).
  CAS PubMed Google Scholar
• Snow, E. T., Foote, R. S. & Mitra, S. Base-pairing properties of O6-methylguanine in template DNA during in vitro DNA replication. J. Biol. Chem. 259, 8095–8100 (1984).
  CAS PubMed Google Scholar
• Branch, P., Aquilina, G., Bignami, M. & Karran, P. Defective mismatch binding and a mutator phenotype in cells tolerant to DNA damage. Nature 362, 652–654 (1993).
  CAS PubMed Google Scholar
• Branch, P., Hampson, R. & Karran, P. DNA mismatch binding defects, DNA damage tolerance, and mutator phenotypes in human colorectal carcinoma cell lines. Cancer Res. 55, 2304–2309 (1995).
  CAS PubMed Google Scholar
• Koi, M. et al. Human chromosome 3 corrects mismatch repair deficiency and microsatellite instability and reduces _N_-methyl-N'-nitro-_N_-nitrosoguanidine tolerance in colon tumor cells with homozygous hMLH1 mutation. Cancer Res. 54, 4308–4312 (1994).
  CAS PubMed Google Scholar
• Loechler, E. L., Green, C. L. & Essigmann, J. M. In vivo mutagenesis by O6-methylguanine built into a unique site in a viral genome. Proc. Natl Acad. Sci. USA 81, 6271–6275 (1984).
  CAS PubMed Google Scholar
• Kawate, H. et al. Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes. Proc. Natl Acad. Sci. USA 95, 5116–5120 (1998). Showed that loss of DNA-MMR in conjunction with loss of MGMT confers tolerance to the killing effects but susceptibility to the mutagenic effects of O 6 -guanine alkylating agents. Several studies have since recapitulated this result using chemotherapy agents, providing a basic model for one form of therapy-related leukaemia.
  CAS PubMed Google Scholar
• Pegg, A. E. Methylation of the O6 position of guanine in DNA is the most likely initiating event in carcinogenesis by methylating agents. Cancer Invest. 2, 223–231 (1984).
  CAS PubMed Google Scholar
• Hampson, R., Humbert, O., Macpherson, P., Aquilina, G. & Karran, P. Mismatch repair defects and O6-methylguanine-DNA methyltransferase expression in acquired resistance to methylating agents in human cells. J. Biol. Chem. 272, 28596–28606 (1997). Demonstrated loss of DNA-MMR in cells treated in vitro with DNA O 6 -guanine alkylating agents.
  CAS PubMed Google Scholar
• Sanada, M., Takagi, Y., Ito, R. & Sekiguchi, M. Killing and mutagenic actions of dacarbazine, a chemotherapeutic alkylating agent, on human and mouse cells: effects of Mgmt and Mlh1 mutations. DNA Repair (Amst) 3, 413–420 (2004).
  CAS Google Scholar
• Gerson, S. L., Phillips, W., Kastan, M., Dumenco, L. L. & Donovan, C. Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU. Blood 88, 1649–1655 (1996). Demonstrated low expression of MGMT in human CD34-positive cells, the target cell for transformation in AML.
  CAS PubMed Google Scholar
• World Health Organisation. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Overall Evaluation of Carcinogenicity: An Updating of Volumes 1 to 42. Supplement 7 (International Agency for Research on Cancer, 1987).
• Travis, L. B. et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. J. Natl Cancer Inst. 94, 182–192 (2002).
  PubMed Google Scholar
• Swann, P. F. et al. Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine. Science 273, 1109–1111 (1996). Showed that the DNA-MMR system recognizes 6-thioguanine lesions incorporated into DNA, which ultimately signal cell death.
  CAS PubMed Google Scholar
• Waters, T. R. & Swann, P. F. Cytotoxic mechanism of 6-thioguanine: hMutSα, the human mismatch binding heterodimer, binds to DNA containing S6- methylthioguanine. Biochemistry (Mosc). 36, 2501–2506 (1997).
  CAS Google Scholar
• Aquilina, G., Zijno, A., Moscufo, N., Dogliotti, E. & Bignami, M. Tolerance to methylnitrosourea-induced DNA damage is associated with 6-thioguanine resistance in CHO cells. Carcinogenesis 10, 1219–1223 (1989).
  CAS PubMed Google Scholar
• Duval, A. et al. The mutator pathway is a feature of immunodeficiency-related lymphomas. Proc. Natl Acad. Sci. USA 101, 5002–5007 (2004).
  CAS PubMed Google Scholar
• Relling, M. V. et al. High incidence of secondary brain tumours after radiotherapy and antimetabolites. Lancet 354, 34–39 (1999). Demonstrated an increased incidence of brain tumours after anti-metabolite therapy in patients with 6-thioguanine metabolism defects.
  CAS PubMed Google Scholar
• Thomsen, J. B. et al. Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism. Cancer 86, 1080–1086 (1999).
  CAS Google Scholar
• Riddel, S. R. in Cancer: Principles and Practice of Oncology (eds Devita, V. T., Hellman, S. & Rosenberg, S.) 2263–2271 (Lippincott Williams and Wilkins, 2004).
  Google Scholar
• Casorelli, I. et al. Drug treatment in the development of mismatch repair defective acute leukemia and myelodysplastic syndrome. DNA Repair (Amst) 2, 547–559 (2003).
  CAS Google Scholar
• Anthoney, D. A., McIlwrath, A. J., Gallagher, W. M., Edlin, A. R. & Brown, R. Microsatellite instability, apoptosis, and loss of p53 function in drug-resistant tumor cells. Cancer Res. 56, 1374–1381 (1996).
  CAS PubMed Google Scholar
• Duckett, D. R. et al. Human MutSα recognizes damaged DNA base pairs containing O6-methylguanine, O4-methylthymine, or the cisplatin-d(GpG) adduct. Proc. Natl Acad. Sci. USA 93, 6443–6447 (1996).
  CAS PubMed Google Scholar
• Aebi, S. et al. Loss of DNA mismatch repair in acquired resistance to cisplatin. Cancer Res. 56, 3087–3090 (1996).
  CAS PubMed Google Scholar
• Drummond, J. T., Anthoney, A., Brown, R. & Modrich, P. Cisplatin and adriamycin resistance are associated with MutLα and mismatch repair deficiency in an ovarian tumor cell line. J. Biol. Chem. 271, 19645–19648 (1996).
  CAS PubMed Google Scholar
• Fink, D. et al. Enrichment for DNA mismatch repair-deficient cells during treatment with cisplatin. Int. J. Cancer 77, 741–746 (1998).
  CAS PubMed Google Scholar
• Strathdee, G., MacKean, M. J., Illand, M. & Brown, R. A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancer. Oncogene 18, 2335–2341 (1999).
  CAS PubMed Google Scholar
• Yamada, M., O'Regan, E., Brown, R. & Karran, P. Selective recognition of a cisplatin–DNA adduct by human mismatch repair proteins. Nucleic Acids Res. 25, 491–496 (1997).
  CAS PubMed PubMed Central Google Scholar
• Gifford, G., Paul, J., Vasey, P. A., Kaye, S. B. & Brown, R. The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients. Clin. Cancer Res. 10, 4420–4426 (2004).
  CAS PubMed Google Scholar
• Travis, L. B. et al. Risk of leukemia after platinum-based chemotherapy for ovarian cancer. N. Engl. J. Med. 340, 351–357 (1999). Showed that women who received radiotherapy and platinum-based chemotherapy had a significantly higher risk of developing leukaemia than those given platinum alone.
  CAS PubMed Google Scholar
• Travis, L. B. et al. Treatment-associated leukemia following testicular cancer. J. Natl Cancer Inst. 92, 1165–1171 (2000).
  CAS PubMed Google Scholar
• Fritzell, J. A. et al. Role of DNA mismatch repair in the cytotoxicity of ionizing radiation. Cancer Res. 57, 5143–5147 (1997).
  CAS PubMed Google Scholar
• DeWeese, T. L. et al. Mouse embryonic stem cells carrying one or two defective Msh2 alleles respond abnormally to oxidative stress inflicted by low-level radiation. Proc. Natl Acad. Sci. USA 95, 11915–11920 (1998).
  CAS PubMed Google Scholar
• Aquilina, G., Crescenzi, M. & Bignami, M. Mismatch repair, G2/M cell cycle arrest and lethality after DNA damage. Carcinogenesis 20, 2317–2326 (1999).
  CAS PubMed Google Scholar
• Yan, T. et al. Loss of DNA mismatch repair imparts defective cdc2 signaling and G2 arrest responses without altering survival after ionizing radiation. Cancer Res. 61, 8290–8297 (2001).
  CAS PubMed Google Scholar
• Franchitto, A. et al. The mammalian mismatch repair protein MSH2 is required for correct MRE11 and RAD51 relocalization and for efficient cell cycle arrest induced by ionizing radiation in G2 phase. Oncogene 22, 2110–2120 (2003).
  CAS PubMed Google Scholar
• Cejka, P., Stojic, L., Marra, G. & Jiricny, J. Is mismatch repair really required for ionizing radiation-induced DNA damage signaling? Nature Genet. 36, 432–433 (2004).
  CAS PubMed Google Scholar
• Papouli, E., Cejka, P. & Jiricny, J. Dependence of the cytotoxicity of DNA-damaging agents on the mismatch repair status of human cells. Cancer Res. 64, 3391–3394 (2004).
  CAS PubMed Google Scholar
• Xu, X. S., Narayanan, L., Dunklee, B., Liskay, R. M. & Glazer, P. M. Hypermutability to ionizing radiation in mismatch repair-deficient, Pms2 knockout mice. Cancer Res. 61, 3775–3780 (2001).
  CAS PubMed Google Scholar
• Colussi, C. et al. The mammalian mismatch repair pathway removes DNA 8-oxodGMP incorporated from the oxidized dNTP pool. Curr. Biol. 12, 912–918 (2002).
  CAS PubMed Google Scholar
• Russo, M. T. et al. The oxidized deoxynucleoside triphosphate pool is a significant contributor to genetic instability in mismatch repair-deficient cells. Mol. Cell Biol. 24, 465–474 (2004).
  CAS PubMed PubMed Central Google Scholar
• Christiansen, D. H., Andersen, M. K. & Pedersen-Bjergaard, J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J. Clin. Oncol. 19, 1405–1413 (2001).
  CAS PubMed Google Scholar
• Pedersen-Bjergaard, J., Pedersen, M., Roulston, D. & Philip, P. Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood 86, 3542–3552 (1995).
  CAS PubMed Google Scholar
• Roy, D., Calaf, G. & Hei, T. K. Frequent allelic imbalance on chromosome 6 and 17 correlate with radiation-induced neoplastic transformation of human breast epithelial cells. Carcinogenesis 22, 1685–1692 (2001).
  CAS PubMed Google Scholar
• Offman, J. et al. Repeated sequences in CASPASE-5 and FANCD2 but not NF1 are targets for mutation in microsatellite-unstable acute leukemia/myelodysplastic syndrome. Mol. Cancer Res. 3, 251–260 (2005).
  CAS PubMed Google Scholar
• Giannini, G. et al. Human MRE11 is inactivated in mismatch repair-deficient cancers. EMBO Rep. 3, 248–254 (2002).
  CAS PubMed PubMed Central Google Scholar
• Worrillow, L. J. & Allan, J. M. Deregulation of homologous recombination DNA repair in alkylating agent-treated stem cell clones: a possible role in the aetiology of chemotherapy-induced leukaemia. Oncogene 7 Nov 2005 (doi: 10.1038/sj.onc.1209208)
• MacDonald, D. et al. Evidence of genetic instability in 3 Gy X-ray-induced mouse leukaemias and 3 Gy X-irradiated haemopoietic stem cells. Intl J. Radiat. Biol. 77, 1023–1031 (2001).
  CAS PubMed Google Scholar
• Plumb, M., Cleary, H. & Wright, E. Genetic instability in radiation-induced leukaemias: mouse models. Intl J. Radiat. Biol. 74, 711–720 (1998).
  CAS PubMed Google Scholar
• Hall, E. J. & Hei, T. K. Genomic instability and bystander effects induced by high-LET radiation. Oncogene 22, 7034–7042 (2003).
  CAS PubMed Google Scholar
• Little, J. B. Genomic instability and radiation. J. Radiol. Prot. 23, 173–181 (2003).
  CAS PubMed Google Scholar
• Little, J. B. Genomic instability and bystander effects: a historical perspective. Oncogene 22, 6978–6987 (2003).
  CAS PubMed Google Scholar
• Cejka, P. et al. Methylation-induced G2/M arrest requires a full complement of the mismatch repair protein hMLH1. EMBO J. 22, 2245–2254 (2003).
  CAS PubMed PubMed Central Google Scholar
• de Wind, N., Dekker, M., Berns, A., Radman, M. & te Riele, H. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82, 321–330 (1995). Demonstrated that loss of DNA-MMR not only confers tolerance to the killing effects of alkylating agents, but also gives rise to hyper-recombination.
  CAS PubMed Google Scholar
• de Wind, N., Dekker, M., van Rossum, A., van der Valk, M. & te Riele, H. Mouse models for hereditary nonpolyposis colorectal cancer. Cancer Res. 58, 248–255 (1998).
  CAS PubMed Google Scholar
• Povey, A. C. et al. DNA alkylation and repair in the large bowel: animal and human studies. J. Nutr. 132, 3518S–3521S (2002).
  CAS PubMed Google Scholar
• Peltomaki, P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J. Clin. Oncol. 21, 1174–1179 (2003).
  CAS PubMed Google Scholar
• Boice, J. D. Jr. et al. Radiation dose and leukemia risk in patients treated for cancer of the cervix. J. Natl Cancer Inst. 79, 1295–1311 (1987). Showed an increasing risk of developing leukaemia with increasing radiation dose to the bone marrow up to 4 Gy, with a subsequent reduction in the risk of developing leukaemia at higher radiation doses.
  PubMed Google Scholar
• Kaldor, J. M. et al. Leukemia following Hodgkin's disease. N. Engl. J. Med. 322, 7–13 (1990).
  CAS PubMed Google Scholar
• Kaldor, J. M. et al. Leukemia following chemotherapy for ovarian cancer. N. Engl. J. Med. 322, 1–6 (1990).
  CAS PubMed Google Scholar
• Gibbons, D. L. et al. An Eμ_–_BCL-2 transgene facilitates leukaemogenesis by ionizing radiation. Oncogene 18, 3870–3877 (1999). Showed that inappropriate inhibition of cell death by overexpression of BCL2 predisposes to radiation-induced leukaemia.
  CAS PubMed Google Scholar
• Kemp, C. J., Wheldon, T. & Balmain, A. p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis. Nature Genet. 8, 66–69 (1994).
  CAS PubMed Google Scholar
• Allan, J. M. et al. Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy. Blood 104, 3872–3877 (2004).
  CAS PubMed Google Scholar
• Travis, L. B. et al. Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. JAMA 290, 465–475 (2003). Demonstrated a reduced risk of subsequently developing breast cancer in those women treated with chest radiotherapy who also received a significant radiation dose to the ovaries or who were also given alkylating agents.
  PubMed Google Scholar
• Bielas, J. H. & Heddle, J. A. Proliferation is necessary for both repair and mutation in transgenic mouse cells. Proc. Natl Acad. Sci. USA 97, 11391–11396 (2000).
  CAS PubMed Google Scholar
• Boice, J. D. Jr., Preston, D., Davis, F. G. & Monson, R. R. Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts. Radiat. Res. 125, 214–222 (1991). Demonstrated that the risk of developing radiogenic breast cancer was inversely proportional to age.
  PubMed Google Scholar
• Dores, G. M. et al. Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years. J. Clin. Oncol. 20, 3484–3494 (2002). Showed that the relative risk of developing solid tumours after Hodgkin disease, particularly breast cancer, decreased with increasing age.
  PubMed Google Scholar
• van Leeuwen, F. E. et al. Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin's disease. J. Natl Cancer Inst. 95, 971–980 (2003). Showed that a smaller number of pre-menopausal years after chest radiotherapy was associated with a lower risk of developing breast cancer.
  PubMed Google Scholar
• Calaf, G. M. & Hei, T. K. Establishment of a radiation- and estrogen-induced breast cancer model. Carcinogenesis 21, 769–776 (2000).
  CAS PubMed Google Scholar
• van Leeuwen, F. E. et al. Roles of radiotherapy and smoking in lung cancer following Hodgkin's disease. J. Natl Cancer Inst. 87, 1530–1537 (1995). Demonstrated a multiplicative association between smoking and radiotherapy on the risk of developing lung cancer.
  CAS PubMed Google Scholar
• Hecht, S. S. DNA adduct formation from tobacco-specific _N_-nitrosamines. Mutat. Res. 424, 127–142 (1999).
  CAS PubMed Google Scholar
• Travis, L. B. et al. Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J. Natl Cancer Inst. 87, 524–530 (1995).
  CAS PubMed Google Scholar
• Birdwell, S. H., Hancock, S. L., Varghese, A., Cox, R. S. & Hoppe, R. T. Gastrointestinal cancer after treatment of Hodgkin's disease. Int. J. Radiat. Oncol. Biol. Phys 37, 67–73 (1997).
  CAS PubMed Google Scholar
• Sancar, A., Lindsey-Boltz, L. A., Unsal-Kacmaz, K. & Linn, S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73, 39–85 (2004).
  CAS PubMed Google Scholar
• Kunkel, T. A. & Erie, D. A. DNA mismatch repair. Annu. Rev. Biochem. 74, 681–710 (2005).
  CAS PubMed Google Scholar
• Ng, A. K. et al. Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors. Blood 100, 1989–1996 (2002).
  CAS PubMed Google Scholar
• Hancock, S. L., Tucker, M. A. & Hoppe, R. T. Breast cancer after treatment of Hodgkin's disease. J. Natl Cancer Inst. 85, 25–31 (1993).
  CAS PubMed Google Scholar
• Swerdlow, A. J. et al. Risk of second malignancy after Hodgkin's disease in a collaborative British cohort: the relation to age at treatment. J. Clin. Oncol. 18, 498–509 (2000).
  CAS PubMed Google Scholar
• Megonigal, M. D. et al. Panhandle PCR strategy to amplify MLL genomic breakpoints in treatment-related leukemias. Proc. Natl Acad. Sci. USA 94, 11583–11588 (1997).
  CAS PubMed Google Scholar