Defective homologous recombination in human cancers

Kastan, 2004, Cell-cycle checkpoints and cancer, Nature, 432, 316, 10.1038/nature03097 Kennedy, 2006, DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes, J Clin Oncol, 24, 3799, 10.1200/JCO.2005.05.4171 Lengauer, 1998, Genetic instabilities in human cancers, Nature, 396, 643, 10.1038/25292 Macaluso, 2005, Modulation of cell cycle components by epigenetic and genetic events, Semin Oncol, 32, 452, 10.1053/j.seminoncol.2005.07.009 Bartkova, 2005, DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis, Nature, 434, 864, 10.1038/nature03482 Lindahl, 1993, Instability and decay of the primary structure of DNA, Nature, 362, 709, 10.1038/362709a0 Khanna, 2001, DNA double-strand breaks: signaling, repair and the cancer connection, Nat Genet, 27, 247, 10.1038/85798 Kaelin, 2005, The concept of synthetic lethality in the context of anticancer therapy, Nat Rev Cancer, 5, 689, 10.1038/nrc1691 Ashworth, 2008, A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair, J Clin Oncol, 26, 3785, 10.1200/JCO.2008.16.0812 Noel, 2003, Poly(ADP-ribose) polymerase (PARP-1) is not involved in DNA double-strand break recovery, BMC Cell Biol, 4, 7, 10.1186/1471-2121-4-7 Haber, 1999, DNA recombination: the replication connection, Trends Biochem Sci, 24, 271, 10.1016/S0968-0004(99)01413-9 Gudmundsdottir, 2006, The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability, Oncogene, 25, 5864, 10.1038/sj.onc.1209874 Bryant, 2005, Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase, Nature, 434, 913, 10.1038/nature03443 Farmer, 2005, Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy, Nature, 434, 917, 10.1038/nature03445 Plummer, 2008, Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors, Clin Cancer Res, 14, 7917, 10.1158/1078-0432.CCR-08-1223 Fong, 2009, Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers, N Engl J Med, 361, 123, 10.1056/NEJMoa0900212 Tuma, 2007, Combining carefully selected drug, patient genetics may lead to total tumor death, J Natl Cancer Inst, 99, 1505, 10.1093/jnci/djm194 Tutt, 2010, Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial, Lancet, 376, 235, 10.1016/S0140-6736(10)60892-6 Drew, 2010, The emerging potential of poly(ADP-ribose) polymerase inhibitors in the treatment of breast cancer, Curr Opin Obstet Gynecol, 22, 67, 10.1097/GCO.0b013e328334ff57 Audeh, 2010, Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial, Lancet, 376, 245, 10.1016/S0140-6736(10)60893-8 McCabe, 2006, Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition, Cancer Res, 66, 8109, 10.1158/0008-5472.CAN-06-0140 Turner, 2004, Hallmarks of ‘BRCAness’ in sporadic cancers, Nat Rev Cancer, 4, 814, 10.1038/nrc1457 Helleday, 2010, Homologous recombination in cancer development, treatment and development of drug resistance, Carcinogenesis, 31, 955, 10.1093/carcin/bgq064 Jacquemont, 2007, Proteasome function is required for DNA damage response and fanconi anemia pathway activation, Cancer Res, 67, 7395, 10.1158/0008-5472.CAN-07-1015 Hartlerode, 2009, Mechanisms of double-strand break repair in somatic mammalian cells, Biochem J, 423, 157, 10.1042/BJ20090942 Paull, 2005, The Mre11/Rad50/Nbs1 complex and its role as a DNA double-strand break sensor for ATM, Cell Cycle, 4, 737, 10.4161/cc.4.6.1715 Zhong, 1999, Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response, Science, 285, 747, 10.1126/science.285.5428.747 You, 2005, ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1, Mol Cell Biol, 25, 5363, 10.1128/MCB.25.13.5363-5379.2005 Chistiakov, 2008, Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients, Acta Oncol, 47, 809, 10.1080/02841860801885969 Sung, 2006, Mechanism of homologous recombination: mediators and helicases take on regulatory functions, Nat Rev Mol Cell Biol, 7, 739, 10.1038/nrm2008 Zhang, 2009, PALB2 links BRCA1 and BRCA2 in the DNA-damage response, Curr Biol, 19, 524, 10.1016/j.cub.2009.02.018 Sy, 2009, PALB2 is an integral component of the BRCA complex required for homologous recombination repair, Proc Natl Acad Sci USA, 106, 7155, 10.1073/pnas.0811159106 Moynahan, 2001, BRCA2 is required for homology-directed repair of chromosomal breaks, Mol Cell, 7, 263, 10.1016/S1097-2765(01)00174-5 Davies, 2001, Role of BRCA2 in control of the RAD51 recombination and DNA repair protein, Mol Cell, 7, 273, 10.1016/S1097-2765(01)00175-7 Cortez, 1999, Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks, Science, 286, 1162, 10.1126/science.286.5442.1162 Bugreev, 2006, Rad54 protein promotes branch migration of Holliday junctions, Nature, 442, 590, 10.1038/nature04889 Wu, 2003, The Bloom’s syndrome helicase suppresses crossing over during homologous recombination, Nature, 426, 870, 10.1038/nature02253 Bohr, 2008, Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance, Trends Biochem Sci, 33, 609, 10.1016/j.tibs.2008.09.003 Ip, 2008, Identification of Holliday junction resolvases from humans and yeast, Nature, 456, 357, 10.1038/nature07470 Hoeijmakers, 2001, Genome maintenance mechanisms for preventing cancer, Nature, 411, 366, 10.1038/35077232 Pellegrini, 2002, Insights into DNA recombination from the structure of a RAD51–BRCA2 complex, Nature, 420, 287, 10.1038/nature01230 Bishop, 2002, Homologous recombination and its role in carcinogenesis, J Biomed Biotechnol, 2, 75, 10.1155/S1110724302204052 Ban, 2001, Chromosomal instability in BRCA1- or BRCA2-defective human cancer cells detected by spontaneous micronucleus assay, Mutat Res, 474, 15, 10.1016/S0027-5107(00)00152-4 Wooster, 2003, Breast and ovarian cancer, N Engl J Med, 348, 2339, 10.1056/NEJMra012284 King, 2003, Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2, Science, 302, 643, 10.1126/science.1088759 Brose, 2002, Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program, J Natl Cancer Inst, 94, 1365, 10.1093/jnci/94.18.1365 Murphy, 2002, Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%, Cancer Res, 62, 3789 Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst 1999;91(15):1310–16. Berman, 1996, A common mutation in BRCA2 that predisposes to a variety of cancers is found in both Jewish Ashkenazi and non-Jewish individuals, Cancer Res, 56, 3409 Narayan, 2003, Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome, Mol Cancer, 2, 24, 10.1186/1476-4598-2-24 Marsit, 2004, Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival, Oncogene, 23, 1000, 10.1038/sj.onc.1207256 Risch, 2006, Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada, J Natl Cancer Inst, 98, 1694, 10.1093/jnci/djj465 Ford, 1998, Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium, Am J Hum Genet, 62, 676, 10.1086/301749 De Leon Matsuda, 2002, BRCA1 and BRCA2 mutations among breast cancer patients from the Philippines, Int J Cancer, 98, 596, 10.1002/ijc.10194 Nedelcu, 2002, BRCA mutations in Italian breast/ovarian cancer families, Eur J Hum Genet, 10, 150, 10.1038/sj.ejhg.5200755 Warner, 1999, Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer, J Natl Cancer Inst, 91, 1241, 10.1093/jnci/91.14.1241 Langston, 1996, BRCA1 mutations in a population-based sample of young women with breast cancer, N Engl J Med, 334, 137, 10.1056/NEJM199601183340301 Malone, 2000, Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases, Cancer, 88, 1393, 10.1002/(SICI)1097-0142(20000315)88:6<1393::AID-CNCR17>3.0.CO;2-P Gonzalez, 1999, Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations, Br J Cancer, 81, 503, 10.1038/sj.bjc.6690722 Ding, 2004, Abnormality of the DNA double-strand-break checkpoint/repair genes, ATM, BRCA1 and TP53, in breast cancer is related to tumour grade, Br J Cancer, 90, 1995, 10.1038/sj.bjc.6601804 Johnson, 2002, Sporadic breast cancer in young women: prevalence of loss of heterozygosity at p53, BRCA1 and BRCA2, Int J Cancer, 98, 205, 10.1002/ijc.10197 Catteau, 2002, BRCA1 methylation: a significant role in tumour development?, Semin Cancer Biol, 12, 359, 10.1016/S1044-579X(02)00056-1 Esteller, 2000, Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors, J Natl Cancer Inst, 92, 564, 10.1093/jnci/92.7.564 Jacinto, 2007, Mutator pathways unleashed by epigenetic silencing in human cancer, Mutagenesis, 22, 247, 10.1093/mutage/gem009 Healey, 2000, A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability, Nat Genet, 26, 362, 10.1038/81691 Auranen, 2003, BRCA2 Arg372Hispolymorphism and epithelial ovarian cancer risk, Int J Cancer, 103, 427, 10.1002/ijc.10814 Liede, 2004, Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature, J Clin Oncol, 22, 735, 10.1200/JCO.2004.05.055 Frank, 2002, Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals, J Clin Oncol, 20, 1480, 10.1200/JCO.20.6.1480 Thorlacius, 1997, Study of a single BRCA2 mutation with high carrier frequency in a small population, Am J Hum Genet, 60, 1079 Thorlacius, 1998, Population-based study of risk of breast cancer in carriers of BRCA2 mutation, Lancet, 352, 1337, 10.1016/S0140-6736(98)03300-5 Ottini, 2003, BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy, Cancer Res, 63, 342 Struewing, 1999, Founder BRCA1/2 mutations among male patients with breast cancer in Israel, Am J Hum Genet, 65, 1800, 10.1086/302678 Struewing, 1995, The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals, Nat Genet, 11, 198, 10.1038/ng1095-198 Rubin, 1998, BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing, Am J Obstet Gynecol, 178, 670, 10.1016/S0002-9378(98)70476-4 Van Der Looij, 2000, Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary, Int J Cancer, 86, 737, 10.1002/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1 Khoo, 2000, Mutational analysis of BRCA1 and BRCA2 genes in Chinese ovarian cancer identifies 6 novel germline mutations, Hum Mutat, 16, 88, 10.1002/1098-1004(200007)16:1<88::AID-HUMU16>3.0.CO;2-G Matsushima, 1995, Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation, Hum Mol Genet, 4, 1953, 10.1093/hmg/4.10.1953 Takahashi, 1995, Mutation analysis of the BRCA1 gene in ovarian cancers, Cancer Res, 55, 2998 Risch, 2001, Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer, Am J Hum Genet, 68, 700, 10.1086/318787 Stratton, 1997, Contribution of BRCA1 mutations to ovarian cancer, N Engl J Med, 336, 1125, 10.1056/NEJM199704173361602 Janezic, 1999, Germline BRCA1 alterations in a population-based series of ovarian cancer cases, Hum Mol Genet, 8, 889, 10.1093/hmg/8.5.889 Foster, 1996, Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer, Cancer Res, 56, 3622 Takahashi, 1996, Mutations of the BRCA2 gene in ovarian carcinomas, Cancer Res, 56, 2738 Pal, 2005, BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases, Cancer, 104, 2807, 10.1002/cncr.21536 Teodoridis, 2005, CpG island methylation of DNA damage response genes in advanced ovarian cancer, Cancer Res, 65, 8961, 10.1158/0008-5472.CAN-05-1187 Hilton, 2002, Inactivation of BRCA1 and BRCA2 in ovarian cancer, J Natl Cancer Inst, 94, 1396, 10.1093/jnci/94.18.1396 Boyd, 2000, Clinicopathologic features of BRCA-linked and sporadic ovarian cancer, JAMA, 283, 2260, 10.1001/jama.283.17.2260 Moslehi, 2000, BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer, Am J Hum Genet, 66, 1259, 10.1086/302853 Muto, 1996, Frequency of the BRCA1 185delAG mutation among Jewish women with ovarian cancer and matched population controls, Cancer Res, 56, 1250 Gotlieb, 1998, Rates of Jewish ancestral mutations in BRCA1 and BRCA2 in borderline ovarian tumors, J Natl Cancer Inst, 90, 995, 10.1093/jnci/90.13.995 Real, 2002, Family history of cancer and germline BRCA2 mutations in sporadic exocrine pancreatic cancer, Gut, 50, 653, 10.1136/gut.50.5.653 Lal, 2000, Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations, Cancer Res, 60, 409 Goggins, 1996, Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas, Cancer Res, 56, 5360 Ozcelik, 1997, Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients, Nat Genet, 16, 17, 10.1038/ng0597-17 Hahn, 2003, BRCA2 germline mutations in familial pancreatic carcinoma, J Natl Cancer Inst, 95, 214, 10.1093/jnci/95.3.214 Thompson, 2002, Cancer Incidence in BRCA1 mutation carriers, J Natl Cancer Inst, 94, 1358, 10.1093/jnci/94.18.1358 van der Heijden, 2006, Does tumorigenesis select for or against mutations of the DNA repair-associated genes BRCA2 and MRE11? Considerations from somatic mutations in microsatellite unstable (MSI) gastrointestinal cancers, BMC Genet, 7, 3, 10.1186/1471-2156-7-3 Edwards, 2003, Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene, Am J Hum Genet, 72, 1, 10.1086/345310 Johannesdottir, 1996, High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients, Cancer Res, 56, 3663 Struewing, 1997, The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews, N Engl J Med, 336, 1401, 10.1056/NEJM199705153362001 Available from: http://clinicaltrials.gov.in. Tutt, 2009, Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer, J Clin Oncol, 27, CRA501, 10.1200/jco.2009.27.18_suppl.cra501 Tutt, 2010, Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial, Lancet, 376, 235, 10.1016/S0140-6736(10)60892-6 Audeh, 2009, Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer, J Clin Oncol, 27, 5500, 10.1200/jco.2009.27.15_suppl.5500 Audeh, 2010, Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial, Lancet, 376, 245, 10.1016/S0140-6736(10)60893-8 Bartsch, 2010, Triple-negative breast cancer, Wien Med Wochenschr, 160, 174, 10.1007/s10354-010-0773-6 O’Shaughnessy, 2009, Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial, J Clin Oncol, 27, 3, 10.1200/jco.2009.27.18_suppl.3 O’Shaughnessy, 2011, Iniparib plus chemotherapy in metastatic triple-negative breast cancer, N Engl J Med, 364, 205, 10.1056/NEJMoa1011418 Gelmon, 2010, Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer [abstract], J Clin Oncol, 28, 3002, 10.1200/jco.2010.28.15_suppl.3002 Nechiporchik N, Lieb KM, Polin L, Peters GJ, Chen A, Ethier SP, LoRusso PM, Burger AM. Preclinical activity of the poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 in combination with irinotecan in ovarian and triple negative breast cancers. Molecular-targeted therapies-preclinical. 22nd EORTC-NCI-AACR symposium on molecular targets and cancer therapeutics. Berlin, Germany; 2010. [Poster number 189]. Wenham R, Sandhu SK, Wilding G, Sun L, Toniatti C, Stroh M, Carpenter C, de-Bono J, Baird R, Schelman WR. First in human trial of a poly(ADP)-ribose polymerase (PARP) inhibitor MK-4827 in advanced cancer patients (p) with antitumor activity in BRCA-deficient and sporadic ovarian cancers. 22nd EORTC-NCI-AACR symposium on molecular targets and cancer therapeutics. Berlin, Germany; 2010. Gatei, 2000, ATM-dependent phosphorylation of nibrin in response to radiation exposure, Nat Genet, 25, 115, 10.1038/75508 Baskaran, 1997, Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation, Nature, 387, 516, 10.1038/387516a0 Siliciano, 1997, DNA damage induces phosphorylation of the amino terminus of p53, Genes Dev, 11, 3471, 10.1101/gad.11.24.3471 Abraham, 2001, Cell cycle checkpoint signaling through the ATM and ATR kinases, Genes Dev, 15, 2177, 10.1101/gad.914401 Zhou, 2000, The DNA damage response: putting checkpoints in perspective, Nature, 408, 433, 10.1038/35044005 McGowan, 2004, The DNA damage response: sensing and signaling, Curr Opin Cell Biol, 16, 629, 10.1016/j.ceb.2004.09.005 Broeks, 2008, The spectrum of ATM missense variants and their contribution to contralateral breast cancer, Breast Cancer Res Treat, 107, 243, 10.1007/s10549-007-9543-6 Milne, 2009, Variants in the ATM gene and breast cancer susceptibility, Genome Med, 1, 12, 10.1186/gm12 Athma, 1996, Molecular genotyping shows that ataxia-telangiectasia heterozygotes are predisposed to breast cancer, Cancer Genet Cytogenet, 92, 130, 10.1016/S0165-4608(96)00328-7 Taylor, 1975, Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity, Nature, 258, 427, 10.1038/258427a0 Swift, 1990, Cancer predisposition of ataxia-telangiectasia heterozygotes, Cancer Genet Cytogenet, 46, 21, 10.1016/0165-4608(90)90004-T Swift, 1991, Incidence of cancer in 161 families affected by ataxia-telangiectasia, N Engl J Med, 325, 1831, 10.1056/NEJM199112263252602 Thompson, 2005, Cancer risks and mortality in heterozygous ATM mutation carriers, J Natl Cancer Inst, 97, 813, 10.1093/jnci/dji141 Easton, 1994, Cancer risks in A-T heterozygotes, Int J Radiat Biol, 66, S177, 10.1080/09553009414552011 Paglia, 2009, ATM germline mutations in women with familial breast cancer and a relative with haematological malignancy, Breast Cancer Res Treat, 119, 443, 10.1007/s10549-009-0396-z Geoffroy-Perez, 2002, Variation in breast cancer risk of heterozygotes for ataxia-telangiectasia according to environmental factors, Int J Cancer, 99, 619, 10.1002/ijc.10367 Larson, 1997, An allelic variant at the ATM locus is implicated in breast cancer susceptibility, Genet Test, 1, 165, 10.1089/gte.1997.1.165 Thorstenson, 2003, Contributions of ATM mutations to familial breast and ovarian cancer, Cancer Res, 63, 3325 Stankovic, 1998, ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer, Am J Hum Genet, 62, 334, 10.1086/301706 Bogdanova, 2008, A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer, Breast Cancer Res Treat, 118, 207, 10.1007/s10549-008-0189-9 Johnson, 2007, Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility, Hum Mol Genet, 16, 1051, 10.1093/hmg/ddm050 Concannon, 2008, Variants in the ATM gene associated with a reduced risk of contralateral breast cancer, Cancer Res, 68, 6486, 10.1158/0008-5472.CAN-08-0134 Geoffroy-Perez, 2001, Cancer risk in heterozygotes for ataxia-telangiectasia, Int J Cancer, 93, 288, 10.1002/ijc.1329 Angele, 2004, ATM polymorphisms as risk factors for prostate cancer development, Br J Cancer, 91, 783, 10.1038/sj.bjc.6602007 Bose, 2009, The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma, J Pathol, 217, 345, 10.1002/path.2487 He, 2008, ATM in oral carcinogenesis: association with clinicopathological features, J Cancer Res Clin Oncol, 134, 1013, 10.1007/s00432-008-0365-7 Stankovic, 1999, Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia, Lancet, 353, 26, 10.1016/S0140-6736(98)10117-4 Moeller, 2011, DNA repair biomarker profiling of head and neck cancer: Ku80 expression predicts locoregional failure and death following radiotherapy, Clin Cancer Res, 17, 2035, 10.1158/1078-0432.CCR-10-2641 Fang, 2001, Analysis of genetic alterations in primary nasopharyngeal carcinoma by comparative genomic hybridization, Genes Chromosomes Cancer, 30, 254, 10.1002/1098-2264(2000)9999:9999<::AID-GCC1086>3.0.CO;2-D Chen, 1999, Chromosomal aberrations in nasopharyngeal carcinoma analyzed by comparative genomic hybridization, Genes Chromosomes Cancer, 25, 169, 10.1002/(SICI)1098-2264(199906)25:2<169::AID-GCC13>3.0.CO;2-I Flanagan, 2009, Gene-body hypermethylation of ATM in peripheral blood DNA of bilateral breast cancer patients, Hum Mol Genet, 18, 1332, 10.1093/hmg/ddp033 Ai, 2004, Ataxia-telangiectasia-mutated (ATM) gene in head and neck squamous cell carcinoma: promoter hypermethylation with clinical correlation in 100 cases, Cancer Epidemiol Biomarkers Prev, 13, 150, 10.1158/1055-9965.EPI-082-3 Lee, 2005, Genetic polymorphisms of ataxia telangiectasia mutated and breast cancer risk, Cancer Epidemiol Biomarkers Prev, 14, 821, 10.1158/1055-9965.EPI-04-0330 Tamimi, 2004, Common ataxia telangiectasia mutated haplotypes and risk of breast cancer: a nested case–control study, Breast Cancer Res, 6, R416, 10.1186/bcr809 Einarsdottir, 2006, Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study, Breast Cancer Res, 8, R67, 10.1186/bcr1623 Baynes, 2007, Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk, Breast Cancer Res, 9, R27, 10.1186/bcr1669 Hickson, 2004, Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM, Cancer Research, 64, 9152, 10.1158/0008-5472.CAN-04-2727 Williamson, 2010, ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors, Mol Cancer Ther, 9, 347, 10.1158/1535-7163.MCT-09-0872 Durocher, 2006, Mutation analysis, characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families, BMC Cancer, 6, 230, 10.1186/1471-2407-6-230 Heikkinen, 2005, Mutation analysis of the ATR gene in breast and ovarian cancer families, Breast Cancer Res, 7, R495, 10.1186/bcr1037 Kontorovich, 2008, Promoter methylation patterns of ATM, ATR, BRCA1, BRCA2 and P53 as putative cancer risk modifiers in Jewish BRCA1/BRCA2 mutation carriers, Breast Cancer Res Treat, 116, 195, 10.1007/s10549-008-0121-3 Menoyo, 2001, Somatic mutations in the DNA damage-response genes ATR and CHK1 in sporadic stomach tumors with microsatellite instability, Cancer Res, 61, 7727 Mironov, 1999, A novel sensitive method to detect frameshift mutations in exonic repeat sequences of cancer-related genes, Carcinogenesis, 20, 2189, 10.1093/carcin/20.11.2189 Lewis, 2005, Heterozygous ATR mutations in mismatch repair-deficient cancer cells have functional significance, Cancer Res, 65, 7091, 10.1158/0008-5472.CAN-05-1019 Vassileva, 2002, Genes involved in DNA repair are mutational targets in endometrial cancers with microsatellite instability, Cancer Res, 62, 4095 Parsons, 1993, Hypermutability and mismatch repair deficiency in RER+ tumor cells, Cell, 75, 1227, 10.1016/0092-8674(93)90331-J Twerdi, 1999, Relative rates of insertion and deletion mutations in a microsatellite sequence in cultured cells, Proc Natl Acad Sci USA, 96, 2875, 10.1073/pnas.96.6.2875 Beale G, Peassland A, Wang L, et al. Evaluation of a novel Ataxia telangiectasia mutated (ATM) and Rad3-related (ATR) inhibitor, NU6027; 2010. Available from: www.ncri.org.uk/ncriconference/2010abstracts Curtin NJ, Beale G, Cliby WA, et al. Chemosensitisation by NU6027, a novel inhibitor of ATR (ataxia telangiectassia mutated and Rad3 related) kinase. In: 102nd AACR meeting 2011, proceedings [abstract 5498]. Taylor, 2004, Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis, DNA Repair (Amst), 3, 1219, 10.1016/j.dnarep.2004.04.009 Aaltonen, 1998, Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease, N Engl J Med, 338, 1481, 10.1056/NEJM199805213382101 Hampel, 2005, Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer), N Engl J Med, 352, 1851, 10.1056/NEJMoa043146 Vilar, 2011, MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers, Cancer Res, 71, 2632, 10.1158/0008-5472.CAN-10-1120 Giannini, 2002, Human MRE11 is inactivated in mismatch repair-deficient cancers, EMBO Rep, 3, 248, 10.1093/embo-reports/kvf044 Heikkinen, 2003, Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility, J Med Genet, 40, e131, 10.1136/jmg.40.12.e131 Heikkinen, 2006, RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability, Carcinogenesis, 27, 1593, 10.1093/carcin/bgi360 Kim, 2001, Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability, Cancer Res, 61, 36, 10.1186/bcr362 Digweed, 2004, Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks, DNA Repair (Amst), 3, 1207, 10.1016/j.dnarep.2004.03.004 Gorski, 2003, Germline 657del5 mutation in the NBS1 gene in breast cancer patients, Int J Cancer, 106, 379, 10.1002/ijc.11231 Cybulski, 2004, NBS1 is a prostate cancer susceptibility gene, Cancer Res, 64, 1215, 10.1158/0008-5472.CAN-03-2502 Steffen, 2004, Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland, Int J Cancer, 111, 67, 10.1002/ijc.20239 Steffen, 2006, Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene mutation, Int J Cancer, 119, 2970, 10.1002/ijc.22280 Steffen, 2006, Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland, Int J Cancer, 119, 472, 10.1002/ijc.21853 Varon, 2001, Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL), Cancer Res, 61, 3570 Medina, 2003, Screening of homologous recombination gene polymorphisms in lung cancer patients reveals an association of the NBS1–185Gln variant and p53 gene mutations, Cancer Epidemiol Biomarkers Prev, 12, 699 Ryk, 2006, Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never- and ever-smokers, Lung cancer, 54, 285, 10.1016/j.lungcan.2006.08.004 Cariveau, 2007, Characterization of an NBS1 C-terminal peptide that can inhibit ataxia telangiectasia mutated (ATM)-mediated DNA damage responses and enhance radiosensitivity, Mol Pharmacol, 72, 320, 10.1124/mol.107.036681 Dupre, 2008, A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex, Nat Chem Biol, 4, 119, 10.1038/nchembio.63 Knights C, Chresta C, Riches L, et al. preclinical evaluation of PARP inhibitor olaparib in homologous recombination deficient (HRD) MRE11 mutant microsatellite instable (MSI) colorectal cancer [abstract]. In: 20th Annual AACR-NCI-EORTC International conference: molecular targets and cancer therapeutics. Boston, MA; 2009 [abstract A114]. Thacker, 2005, The RAD51 gene family, genetic instability and cancer, Cancer Lett, 219, 125, 10.1016/j.canlet.2004.08.018 Raderschall, 2002, Elevated levels of Rad51 recombination protein in tumor cells, Cancer Res, 62, 219 Connell, 2006, Pilot study examining tumor expression of RAD51 and clinical outcomes in human head cancers, Int J Oncol, 28, 1113 Qiao, 2005, High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients, Br J Cancer, 93, 137, 10.1038/sj.bjc.6602665 Hannay, 2007, Rad51 overexpression contributes to chemoresistance in human soft tissue sarcoma cells: a role for p53/activator protein 2 transcriptional regulation, Mol Cancer Ther, 6, 1650, 10.1158/1535-7163.MCT-06-0636 Mitra, 2009, Overexpression of RAD51 occurs in aggressive prostatic cancer, Histopathology, 55, 696, 10.1111/j.1365-2559.2009.03448.x Maacke, 2002, Autoantibodies in sera of pancreatic cancer patients identify recombination factor Rad51 as a tumour-associated antigen, J Cancer Res Clin Oncol, 128, 219, 10.1007/s00432-001-0321-2 Willers, 2009, Utility of DNA repair protein foci for the detection of putative BRCA1 pathway defects in breast cancer biopsies, Mol Cancer Res, 7, 1304, 10.1158/1541-7786.MCR-09-0149 Graeser, 2010, A marker of homologous recombination predicts pathologic complete response to neoadjuvant chemotherapy in primary breast cancer, Clin Cancer Res, 16, 6159, 10.1158/1078-0432.CCR-10-1027 Barlund, 2000, Multiple genes at 17q23 undergo amplification and overexpression in breast cancer, Cancer Res, 60, 5340 Wu, 2000, 17q23 amplifications in breast cancer involve the PAT1, RAD51C, PS6K, and SIGma1B genes, Cancer Res, 60, 5371 Yoshikawa, 2000, Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast carcinomas, Int J Cancer, 88, 28, 10.1002/1097-0215(20001001)88:1<28::AID-IJC5>3.0.CO;2-4 Munshi, 2004, Identification of genes modulated in multiple myeloma using genetically identical twin samples, Blood, 103, 1799, 10.1182/blood-2003-02-0402 Levy-Lahad, 2001, A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers, Proc Natl Acad Sci USA, 98, 3232, 10.1073/pnas.051624098 Kadouri, 2004, A single-nucleotide polymorphism in the RAD51 gene modifies breast cancer risk in BRCA2 carriers, but not in BRCA1 carriers or noncarriers, Br J Cancer, 90, 2002, 10.1038/sj.bjc.6601837 Seedhouse, 2004, Polymorphisms in genes involved in homologous recombination repair interact to increase the risk of developing acute myeloid leukemia, Clin Cancer Res, 10, 2675, 10.1158/1078-0432.CCR-03-0372 Jawad, 2006, Polymorphisms in human homeobox HLX1 and DNA repair RAD51 genes increase the risk of therapy-related acute myeloid leukemia, Blood, 108, 3916, 10.1182/blood-2006-05-022921 Liu, 1998, XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages, Mol Cell, 1, 783, 10.1016/S1097-2765(00)80078-7 Kuschel, 2002, Variants in DNA double-strand break repair genes and breast cancer susceptibility, Hum Mol Genet, 11, 1399, 10.1093/hmg/11.12.1399 Garcia-Closas, 2006, Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses, Hum Genet, 119, 376, 10.1007/s00439-006-0135-z Rafii, 2002, A potential role for the XRCC2 R188H polymorphic site in DNA-damage repair and breast cancer, Hum Mol Genet, 11, 1433, 10.1093/hmg/11.12.1433 Auranen, 2005, Polymorphisms in DNA repair genes and epithelial ovarian cancer risk, Int J Cancer, 117, 611, 10.1002/ijc.21047 Winsey, 2000, A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer, Cancer Res, 60, 5612 Sturgis, 2005, Radiation response genotype and risk of differentiated thyroid cancer: a case–control analysis, Laryngoscope, 115, 938, 10.1097/01.MLG.0000163765.88158.86 Matullo, 2001, DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case–control study, Int J Cancer, 92, 562, 10.1002/ijc.1228 Zienolddiny, 2006, Polymorphisms of DNA repair genes and risk of non-small cell lung cancer, Carcinogenesis, 27, 560, 10.1093/carcin/bgi232 Asakawa, 2010, Prediction of breast cancer sensitivity to neoadjuvant chemotherapy based on status of DNA damage repair proteins, Breast Cancer Res, 12, R17, 10.1186/bcr2486 Mukhopadhyay, 2010, Development of a functional assay for homologous recombination status in primary cultures of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase inhibitors, Clin Cancer Res, 16, 2344, 10.1158/1078-0432.CCR-09-2758 Ohnishi, 1998, In vitro and in vivo potentiation of radiosensitivity of malignant gliomas by antisense inhibition of the RAD51 gene, Biochem Biophys Res Commun, 245, 319, 10.1006/bbrc.1998.8440 Collis, 2001, Ribozyme minigene-mediated RAD51 down-regulation increases radiosensitivity of human prostate cancer cells, Nucleic Acids Res, 29, 1534, 10.1093/nar/29.7.1534 Ito, 2005, Rad51 siRNA delivered by HVJ envelope vector enhances the anti-cancer effect of cisplatin, J Gene Med, 7, 1044, 10.1002/jgm.753 Alter, 1996, Fanconi’s anemia and malignancies, Am J Hematol, 53, 99, 10.1002/(SICI)1096-8652(199610)53:2<99::AID-AJH7>3.0.CO;2-Z Kennedy, 2005, The Fanconi Anemia/BRCA pathway: new faces in the crowd, Genes Dev, 19, 2925, 10.1101/gad.1370505 Kutler, 2003, A 20-year perspective on the International Fanconi Anemia Registry (IFAR), Blood, 101, 1249, 10.1182/blood-2002-07-2170 Howlett, 2002, Biallelic inactivation of BRCA2 in Fanconi anemia, Science, 297, 606, 10.1126/science.1073834 Moldovan, 2009, How the fanconi anemia pathway guards the genome, Annu Rev Genet, 43, 223, 10.1146/annurev-genet-102108-134222 Thompson, 2005, Unraveling the Fanconi anemia-DNA repair connection, Nat Genet, 37, 921, 10.1038/ng0905-921 Hinz, 2006, The Fanconi anemia pathway limits the severity of mutagenesis, DNA Repair (Amst), 5, 875, 10.1016/j.dnarep.2006.05.039 Taniguchi, 2002, S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51, Blood, 100, 2414, 10.1182/blood-2002-01-0278 Auerbach, 1991, Leukemia and preleukemia in Fanconi anemia patients. A review of the literature and report of the International Fanconi Anemia Registry, Cancer Genet Cytogenet, 51, 1, 10.1016/0165-4608(91)90002-C Alter, 2003, Cancer in Fanconi anemia, 1927–2001, Cancer, 97, 425, 10.1002/cncr.11046 Offit, 2003, Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia, J Natl Cancer Inst, 95, 1548, 10.1093/jnci/djg072 Hirsch, 2004, Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood, Blood, 103, 2554, 10.1182/blood-2003-06-1970 Condie, 2002, Analysis of the Fanconi anaemia complementation group A gene in acute myeloid leukaemia, Leuk Lymphoma, 43, 1849, 10.1080/1042819021000009274 Tischkowitz, 2004, Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia, Leukemia, 18, 420, 10.1038/sj.leu.2403280 Seal, 2006, Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles, Nat Genet, 38, 1239, 10.1038/ng1902 Couch, 2005, Germ line Fanconi anemia complementation group C mutations and pancreatic cancer, Cancer Res, 65, 383, 10.1158/0008-5472.383.65.2 van der Heijden, 2004, Functional defects in the fanconi anemia pathway in pancreatic cancer cells, Am J Pathol, 165, 651, 10.1016/S0002-9440(10)63329-9 Xie, 2000, Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells, Br J Haematol, 111, 1057, 10.1111/j.1365-2141.2000.02450.x Olopade, 2003, FANCF methylation contributes to chemoselectivity in ovarian cancer, Cancer Cell, 3, 417, 10.1016/S1535-6108(03)00111-9 Dhillon, 2004, CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin, Mol Cancer, 3, 33, 10.1186/1476-4598-3-33 Taniguchi, 2003, Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors, Nat Med, 9, 568, 10.1038/nm852 Narayan, 2004, Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer, Cancer Res, 64, 2994, 10.1158/0008-5472.CAN-04-0245 Kennedy, 2007, Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated, J Clin Invest, 117, 1440, 10.1172/JCI31245 Jazaeri, 2002, Gene expression profiles of BRCA1-linked, BRCA2-linked, and sporadic ovarian cancers, J Natl Cancer Inst, 94, 990, 10.1093/jnci/94.13.990 Konstantinopoulos, 2010, Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer, J Clin Oncol, 28, 3555, 10.1200/JCO.2009.27.5719 Alexander, 2010, DNA repair protein biomarkers associated with time to recurrence in triple-negative breast cancer, Clin Cancer Res, 16, 5796, 10.1158/1078-0432.CCR-10-0292 Ahluwalia, 2001, DNA methylation in ovarian cancer. II. Expression of DNA methyltransferases in ovarian cancer cell lines and normal ovarian epithelial cells, Gynecol Oncol, 82, 299, 10.1006/gyno.2001.6284 Gaymes, 2009, Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes, Haematologica, 94, 638, 10.3324/haematol.2008.001933 Ohashi, 2005, Fanconi anemia complementation group D2 (FANCD2) functions independently of BRCA2- and RAD51-associated homologous recombination in response to DNA damage, J Biol Chem, 280, 14877, 10.1074/jbc.M414669200 Gottipati, 2010, Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells, Cancer Res, 70, 5389, 10.1158/0008-5472.CAN-09-4716 Wang, 2005, Complex H2AX phosphorylation patterns by multiple kinases including ATM and DNA-PK in human cells exposed to ionizing radiation and treated with kinase inhibitors, J Cell Physiol, 202, 492, 10.1002/jcp.20141 de Bono, 2011, Poly(ADP-ribose) polymerase (PARP) inhibitors: exploiting a synthetic lethal strategy in the clinic, CA: Cancer J Clin, 61, 31, 10.3322/caac.20095 Koyanagi, 2006, Association of circulating tumor cells with serum tumor-related methylated DNA in peripheral blood of melanoma patients, Cancer Res, 66, 6111, 10.1158/0008-5472.CAN-05-4198 Yap, 2010, Envisioning the future of early anticancer drug development, Nat Rev Cancer, 10, 514, 10.1038/nrc2870 Bryant, 2006, Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair, Nucleic Acids Res, 34, 1685, 10.1093/nar/gkl108 Gaymes, 2008, Chromosomal instability syndromes are sensitive to poly ADP-ribose polymerase inhibitors, Haematologica, 93, 1886, 10.3324/haematol.13201 Mukhopadhyay, 2010, Development of a functional assay for homologous recombination status in primary cultures of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase inhibitors, Clin Cancer Res, 16, 2344, 10.1158/1078-0432.CCR-09-2758