Synthetic genetic targeting of genome instability in cancer

Cancers

Volumn 5, Issue 3, 2013, Pages 739-761

  Sajesh, Babu V ^a   Guppy, Brent J ^a   McManus, Kirk J ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Cancer; Cancer therapy; Genome instability; Oncogene; Synthetic dosage lethality; Synthetic genetic approach; Synthetic lethality; Tumor suppressor gene

Indexed keywords

DNA; INIPARIB; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OLAPARIB;

ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CELL; CANCER CHEMOTHERAPY; CANCER GENETICS; CANCER STAGING; CARCINOGENESIS; CHROMOSOMAL INSTABILITY; CLINICAL TRIAL (TOPIC); DNA REPAIR; DRUG EFFICACY; DRUG MEGADOSE; DRUG TARGETING; EPIGENETICS; GENE EXPRESSION; GENE FUNCTION; GENE INTERACTION; GENE SILENCING; GENE TARGETING; GENETIC ANALYSIS; GENETIC HETEROGENEITY; GENETIC PARAMETERS; GENOMIC INSTABILITY; HUMAN; LOW DRUG DOSE; MALIGNANT NEOPLASTIC DISEASE; MALIGNANT TRANSFORMATION; MICROSATELLITE INSTABILITY; NONHUMAN; ONCOGENE; OUTCOME ASSESSMENT; OVARY CANCER; PERSONALIZED MEDICINE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SOLID TUMOR; SOMATIC MUTATION; SYNTHETIC DOSAGE LETHALITY; SYNTHETIC LETHALITY; TUMOR SUPPRESSOR GENE;

EID: 84879592166     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers5030739     Document Type: Review

References (123)

1. Ferlay, J.S.H.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Globocan 2008 v2.0, Cancer Incidence And Mortality Worldwide: Iarc Cancerbase No. 10.: International Agency for Research on Cancer, Lyon, France, 2010.
2. Cahill, D.P.; Kinzler, K.W.; Vogelstein, B.; Lengauer, C. Genetic instability and Darwinian selection in tumours. Trends Cell Biol. 1999, 9, M57-M60.
3. Lengauer, C.; Kinzler, K.W.; Vogelstein, B. Genetic instabilities in human cancers. Nature 1998, 396, 643-649.
4. Rajagopalan, H.; Jallepalli, P.V.; Rago, C.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Lengauer, C. Inactivation of hcdc4 can cause chromosomal instability. Nature 2004, 428, 77-81.
5. Issa, J.P. Cpg island methylator phenotype in cancer. Nat. Rev. Cancer 2004, 4, 988-993.
6. Boyer, J.C.; Umar, A.; Risinger, J.I.; Lipford, J.R.; Kane, M.; Yin, S.; Barrett, J.C.; Kolodner, R.D.; Kunkel, T.A. Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines. Cancer Res. 1995, 55, 6063-6070.
7. Gazzoli, I.; Loda, M.; Garber, J.; Syngal, S.; Kolodner, R.D. A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the mlh1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instabilityhigh tumor. Cancer Res. 2002, 62, 3925-3928.
8. Loeb, L.A. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991, 51, 3075-3079.
9. Loeb, L.A. A mutator phenotype in cancer. Cancer Res. 2001, 61, 3230-3239.
10. Loeb, L.A.; Bielas, J.H.; Beckman, R.A. Cancers exhibit a mutator phenotype: Clinical implications. Cancer Res. 2008, 68, 3551-3557.
11. Wahlberg, S.S.; Schmeits, J.; Thomas, G.; Loda, M.; Garber, J.; Syngal, S.; Kolodner, R.D. Fox, E. Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line msh2 and mlh1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res. 2002, 62, 3485-3492.
12. Bae, J.M.; Kim, J.H.; Kang, G.H. Epigenetic alterations in colorectal cancer: The CpG island methylator phenotype. Histol. Histopathol. 2013, 28, 585-595.
13. Baylin, S.B.; Jones, P.A. A decade of exploring the cancer epigenome-Biological and translational implications. Nat. Rev. Cancer 2011, 11, 726-734.
14. Feinberg, A.P.; Tycko, B. The history of cancer epigenetics. Nat. Rev. Cancer 2004, 4, 143-153.
15. Lengauer, C.; Kinzler, K.W.; Vogelstein, B. Genetic instability in colorectal cancers. Nature 1997, 386, 623-627.
16. Beheshti, B.; Park, P.C.; Sweet, J.M.; Trachtenberg, J.; Jewett, M.A.; Squire, J.A. Evidence of chromosomal instability in prostate cancer determined by spectral karyotyping (sky) and interphase fish analysis. Neoplasia 2001, 3, 62-69.
17. Burrell, R.A.; McClelland, S.E.; Endesfelder, D.; Groth, P.; Weller, M.C.; Shaikh, N.; Domingo, E.; Kanu, N.; Dewhurst, S.M.; Gronroos, E., et al. Replication stress links structural and numerical cancer chromosomal instability. Nature 2013, 494, 492-496.
18. Mai, S.; Hanley-Hyde, J.; Rainey, G.J.; Kuschak, T.I.; Paul, J.T.; Littlewood, T.D.; Mischak, H.; Stevens, L.M.; Henderson, D.W.; Mushinski, J.F. Chromosomal and extrachromosomal instability of the cyclin d2 gene is induced by myc overexpression. Neoplasia 1999, 1, 241-252.
19. Sjoblom, T.; Jones, S.; Wood, L.D.; Parsons, D.W.; Lin, J.; Barber, T.D.; Mandelker, D.; Leary, R.J.; Ptak, J.; Silliman, N., et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314, 268-274.
20. Barretina, J.; Taylor, B.S.; Banerji, S.; Ramos, A.H.; Lagos-Quintana, M.; Decarolis, P.L. Shah, K.; Socci, N.D.; Weir, B.A.; Ho, A., et al. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat. Genet. 2010, 42, 715-721.
21. Taylor, B.S.; Schultz, N.; Hieronymus, H.; Gopalan, A.; Xiao, Y.; Carver, B.S.; Arora, V.K.; Kaushik, P.; Cerami, E.; Reva, B., et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 2010, 18, 11-22.
22. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011, 474, 609-615.
23. Parsons, D.W.; Li, M.; Zhang, X.; Jones, S.; Leary, R.J.; Lin, J.C.; Boca, S.M.; Carter, H.; Samayoa, J.; Bettegowda, C., et al. The genetic landscape of the childhood cancer medulloblastoma. Science 2011, 331, 435-439.
24. Cancer Genome Atlas Research Network. Comprehensive molecular portraits of human breasttumours. Nature 2012, 490, 61-70.
25. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012, 487, 330-337.
26. Cancer Genome Atlas Research Network; Hammerman, P.S.; Hayes, D.N.; Wilkerson, M.D.; Schultz, N.; Bose, R.; Chu, A.; Collisson, E.A.; Cope, L.; Creighton, C.J., et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012, 489, 519-525.
27. Welch, J.S.; Ley, T.J.; Link, D.C.; Miller, C.A.; Larson, D.E.; Koboldt, D.C.; Wartman, L.D.; Lamprecht, T.L.; Liu, F.; Xia, J., et al. The origin and evolution of mutations in acute myeloid leukemia. Cell 2012, 150, 264-278.
28. Choi, C.M.; Seo, K.W.; Jang, S.J.; Oh, Y.M.; Shim, T.S.; Kim, W.S.; Lee, D.S.; Lee, S.D. Chromosomal instability is a risk factor for poor prognosis of adenocarcinoma of the lung: Fluorescence in situ hybridization analysis of paraffin-embedded tissue from korean patients. Lung Cancer 2009, 64, 66-70.
29. Heilig, C.E.; Loffler, H.; Mahlknecht, U.; Janssen, J.W.; Ho, A.D.; Jauch, A.; Kramer, A., Chromosomal instability correlates with poor outcome in patients with myelodysplastic syndromes irrespectively of the cytogenetic risk group. J. Cell. Mol. Med. 2010, 14, 895-902.
30. Murayama-Hosokawa, S.; Oda, K.; Nakagawa, S.; Ishikawa, S.; Yamamoto, S.; Shoji, K. Ikeda, Y.; Uehara, Y.; Fukayama, M.; McCormick, F., et al. Genome-wide single-nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in the pi3-kinase pathway. Oncogene 2010, 29, 1897-1908.
31. Nakamura, H.; Saji, H.; Idiris, A.; Kawasaki, N.; Hosaka, M.; Ogata, A.; Saijo, T.; Kato, H. Chromosomal instability detected by fluorescence in situ hybridization in surgical specimens of non-small cell lung cancer is associated with poor survival. Clin. Cancer Res. 2003, 9, 2294-2299.
32. Sato, H.; Uzawa, N.; Takahashi, K.; Myo, K.; Ohyama, Y.; Amagasa, T. Prognostic utility of chromosomal instability detected by fluorescence in situ hybridization in fine-needle aspirates from oral squamous cell carcinomas. BMC Cancer 2010, 10, 182.
33. Suehiro, Y.; Okada, T.; Okada, T.; Anno, K.; Okayama, N.; Ueno, K.; Hiura, M.; Nakamura, M.; Kondo, T.; Oga, A., et al. Aneuploidy predicts outcome in patients with endometrial carcinoma and is related to lack of cdh13 hypermethylation. Clin. Cancer Res. 2008, 14, 3354-3361.
34. Tilly, H.; Rossi, A.; Stamatoullas, A.; Lenormand, B.; Bigorgne, C.; Kunlin, A.; Monconduit, M.; Bastard, C. Prognostic value of chromosomal abnormalities in follicular lymphoma. Blood 1994, 84, 1043-1049.
35. Walther, A.; Houlston, R.; Tomlinson, I., Association between chromosomal instability and prognosis in colorectal cancer: A meta-analysis. Gut 2008, 57, 941-950.
36. Yoo, J.W.; Seo, K.W.; Jang, S.J.; Oh, Y.M.; Shim, T.S.; Kim, W.S.; Lee, D.S.; Lee, S.D. Choi, C.M. The relationship between the presence of chromosomal instability and prognosis of squamous cell carcinoma of the lung: Fluorescence in situ hybridization analysis of paraffin-embedded tissue from 47 korean patients. J. Korean Med. Sci. 2010, 25, 863-867.
37. Kinzler, K.W.; Vogelstein, B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 1997, doi:10.1038/386761a0.
38. Farnebo, M.; Bykov, V.J.; Wiman, K.G. The p53 tumor suppressor: A master regulator of diverse cellular processes and therapeutic target in cancer. Biochem. Biophys. Res. Commun. 2010, 396, 85-89.
39. Chinnam, M.; Goodrich, D.W. Rb1, development, and cancer. Curr. Top. Dev. Biol. 2011, 94, 129-169.
40. Vermeij, J.; Teugels, E.; Bourgain, C.; Xiangming, J.; in't Veld, P.; Ghislain, V.; Neyns, B.; de Greve, J., Genomic activation of the EGFR and HER2-neu genes in a significant proportion of invasive epithelial ovarian cancers. BMC Cancer 2008, 8, 3.
41. Baselga, J.; Swain, S.M. Novel anticancer targets: Revisiting ERBB2 and discovering ERBB3. Nat. Rev. Cancer 2009, 9, 463-475.
42. Tsuda, H.; Hirohashi, S.; Hirota, T.; Shimosato, Y. Alterations in copy number of c-erbb-2 and c-myc proto-oncogenes in advanced stage of human breast cancer. Acta Pathol. Jpn. 1991, 41, 19-23.
43. Delgado, M.D.; Albajar, M.; Gomez-Casares, M.T.; Batlle, A.; Leon, J. Myc oncogene in myeloid neoplasias. Clin. Transl. Oncol. 2013, 15, 87-94.
44. Leon, J.; Ferrandiz, N.; Acosta, J.C.; Delgado, M.D. Inhibition of cell differentiation: A critical mechanism for myc-mediated carcinogenesis? Cell Cycle 2009, 8, 1148-1157.
45. Liebermann, D.A.; Hoffman, B. Differentiation primary response genes and proto-oncogenes as positive and negative regulators of terminal hematopoietic cell differentiation. Stem Cells 1994, 12, 352-369.
46. Johnson, L.; Mercer, K.; Greenbaum, D.; Bronson, R.T.; Crowley, D.; Tuveson, D.A.; Jacks, T. Somatic activation of the k-ras oncogene causes early onset lung cancer in mice. Nature 2001, 410, 1111-1116.
47. Aguirre, A.J.; Bardeesy, N.; Sinha, M.; Lopez, L.; Tuveson, D.A.; Horner, J.; Redston, M.S.; DePinho, R.A. Activated kras and ink4a/arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 2003, 17, 3112-3126.
48. Haigis, K.M.; Kendall, K.R.; Wang, Y.; Cheung, A.; Haigis, M.C.; Glickman, J.N. Niwa-Kawakita, M.; Sweet-Cordero, A.; Sebolt-Leopold, J.; Shannon, K.M., et al. Differential effects of oncogenic k-ras and n-ras on proliferation, differentiation and tumor progression in the colon. Nat. Genet. 2008, 40, 600-608.
49. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646-674.
50. Dobzhansky, T. Genetics of natural populations. XIII. Recombination and variability in populations of drosophila pseudoobscura. Genetics 1946, 31, 269-290.
51. Kaelin, W.G., Jr. The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer 2005, 5, 689-698.
52. McManus, K.J.; Barrett, I.J.; Nouhi, Y.; Hieter, P. Specific synthetic lethal killing of rad54b-deficient human colorectal cancer cells by fen1 silencing. Proc. Natl. Acad. Sci. USA 2009, 106, 3276-3281.
53. Van Pel, D.M.; Barrett, I.J.; Shimizu, Y.; Sajesh, B.V.; Guppy, B.J.; Pfeifer, T.; McManus, K.J.; Hieter, P. An evolutionarily conserved synthetic lethal interaction network identifies fen1 as a broad-spectrum target for anticancer therapeutic development. PLoS Genet. 2013, 9, e1003254.
54. Hartwell, L.H.; Szankasi, P.; Roberts, C.J.; Murray, A.W.; Friend, S.H. Integrating genetic approaches into the discovery of anticancer drugs. Science 1997, 278, 1064-1068.
55. Kaelin, W.G., Jr. Choosing anticancer drug targets in the postgenomic era. J. Clin. Invest. 1999, 104, 1503-1506.
56. Friend, S.H.; Oliff, A. Emerging uses for genomic information in drug discovery. N. Engl. J. Med. 1998, 338, 125-126.
57. Roy, R.; Chun, J.; Powell, S.N. Brca1 and brca2: Different roles in a common pathway of genome protection. Nat. Rev. Cancer 2012, 12, 68-78.
58. El-Khamisy, S.F.; Masutani, M.; Suzuki, H.; Caldecott, K.W. A requirement for parp-1 for the assembly or stability of xrcc1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res. 2003, 31, 5526-5533.
59. Okano, S.; Lan, L.; Caldecott, K.W.; Mori, T.; Yasui, A. Spatial and temporal cellular responses to single-strand breaks in human cells. Mol. Cell. Biol. 2003, 23, 3974-3981.
60. Strom, C.E.; Johansson, F.; Uhlen, M.; Szigyarto, C.A.; Erixon, K.; Helleday, T. Poly (adp-ribose) polymerase (parp) is not involved in base excision repair but parp inhibition traps a single-strand intermediate. Nucleic Acids Res. 2011, 39, 3166-3175.
61. Schreiber, V.; Dantzer, F.; Ame, J.C.; de Murcia, G. Poly(adp-ribose): Novel functions for an old molecule. Nat. Rev. Mol. Cell Biol. 2006, 7, 517-528.
62. Kraus, W.L.; Hottiger, M.O. PARP-1 and gene regulation: Progress and puzzles. Mol. Aspects Med. 2013, doi:10.1016/j.mam.2013.01.005.
63. Kuzminov, A. Single-strand interruptions in replicating chromosomes cause double-strand breaks. Proc. Natl. Acad. Sci. USA 2001, 98, 8241-8246.
64. Bryant, H.E.; Schultz, N.; Thomas, H.D.; Parker, K.M.; Flower, D.; Lopez, E.; Kyle, S.; Meuth, M.; Curtin, N.J.; Helleday, T. Specific killing of brca2-deficient tumours with inhibitors of poly(adp-ribose) polymerase. Nature 2005, 434, 913-917.
65. Farmer, H.; McCabe, N.; Lord, C.J.; Tutt, A.N.; Johnson, D.A.; Richardson, T.B.; Santarosa, M.; Dillon, K.J.; Hickson, I.; Knights, C., et al. Targeting the DNA repair defect in brca mutant cells as a therapeutic strategy. Nature 2005, 434, 917-921.
66. Rouleau, M.; Patel, A.; Hendzel, M.J.; Kaufmann, S.H.; Poirier, G.G. Parp inhibition: Parp1 and beyond. Nat. Rev. Cancer 2010, 10, 293-301.
67. Papeo, G.; Casale, E.; Montagnoli, A.; Cirla, A. Parp inhibitors in cancer therapy: An update. Expert Opin. Ther. Pat. 2013, 23, 503-514.
68. Glendenning, J.; Tutt, A. Parp inhibitors-Current status and the walk towards early breast cancer. Breast 2011, 20, S12-S19.
69. Fong, P.C.; Boss, D.S.; Yap, T.A.; Tutt, A.; Wu, P.; Mergui-Roelvink, M.; Mortimer, P. Swaisland, H.; Lau, A.; O'Connor, M.J, et al. Inhibition of poly(adp-ribose) polymerase in tumors from brca mutation carriers. N. Engl. J. Med. 2009, 361, 123-134.
70. Orlando, L.; Schiavone, P.; Fedele, P.; Calvani, N.; Nacci, A.; Cinefra, M.; D'Amico, M. Mazzoni, E.; Marino, A.; Sponziello, F., et al. Poly (adp-ribose) polymerase (parp): Rationale, preclinical and clinical evidences of its inhibition as breast cancer treatment. Expert Opin. Ther. Targets 2012, 16, S83-S89.
71. Audeh, M.W.; Carmichael, J.; Penson, R.T.; Friedlander, M.; Powell, B.; Bell-McGuinn, K.M.; Scott, C.; Weitzel, J.N.; Oaknin, A.; Loman, N., et al. Oral poly(adp-ribose) polymerase inhibitor olaparib in patients with brca1 or brca2 mutations and recurrent ovarian cancer: A proof-of-concept trial. Lancet 2010, 376, 245-251.
72. Fogelman, D.R.; Wolff, R.A.; Kopetz, S.; Javle, M.; Bradley, C.; Mok, I.; Cabanillas, F. Abbruzzese, J.L. Evidence for the efficacy of iniparib, a parp-1 inhibitor, in brca2-associated pancreatic cancer. Anticancer Res. 2011, 31, 1417-1420.
73. O'Shaughnessy, J.; Osborne, C.; Pippen, J.E.; Yoffe, M.; Patt, D.; Rocha, C.; Koo, I.C. Sherman, B.M.; Bradley, C. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N. Engl. J. Med. 2011, 364, 205-214.
74. Patel, A.G.; de Lorenzo, S.B.; Flatten, K.S.; Poirier, G.G.; Kaufmann, S.H. Failure of iniparib to inhibit poly(adp-ribose) polymerase in vitro. Clin. Cancer Res. 2012, 18, 1655-1662.
75. Liu, X.; Shi, Y.; Maag, D.X.; Palma, J.P.; Patterson, M.J.; Ellis, P.A.; Surber, B.W.; Ready, D.B.; Soni, N.B.; Ladror, U.S., et al. Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide parp inhibitor. Clin. Cancer Res. 2012, 18, 510-523.
76. Caldecott, K.W. Single-strand break repair and genetic disease. Nat. Rev. Genet. 2008, 9, 619-631.
77. Lieber, M.R. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu. Rev. Biochem. 2010, 79, 181-211.
78. Li, X.; Heyer, W.D. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008, 18, 99-113.
79. Curtin, N.J. DNA repair dysregulation from cancer driver to therapeutic target. Nat. Rev. Cancer 2012, 12, 801-817.
80. Fiedler, D.; Braberg, H.; Mehta, M.; Chechik, G.; Cagney, G.; Mukherjee, P.; Silva, A.C. Shales, M.; Collins, S.R.; van Wageningen, S., et al. Functional organization of the s. Cerevisiae phosphorylation network. Cell 2009, 136, 952-963.
81. Lin, Y.Y.; Qi, Y.; Lu, J.Y.; Pan, X.; Yuan, D.S.; Zhao, Y.; Bader, J.S.; Boeke, J.D. A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation. Genes Dev. 2008, 22, 2062-2074.
82. Montpetit, B.; Thorne, K.; Barrett, I.; Andrews, K.; Jadusingh, R.; Hieter, P.; Measday, V. Genome-wide synthetic lethal screens identify an interaction between the nuclear envelope protein, apq12p, and the kinetochore in saccharomyces cerevisiae. Genetics 2005, 171, 489-501.
83. Zhao, R.; Davey, M.; Hsu, Y.C.; Kaplanek, P.; Tong, A.; Parsons, A.B.; Krogan, N.; Cagney, G.; Mai, D.; Greenblatt, J., et al. Navigating the chaperone network: An integrative map of physical and genetic interactions mediated by the hsp90 chaperone. Cell 2005, 120, 715-727.
84. Lehner, B.; Crombie, C.; Tischler, J.; Fortunato, A.; Fraser, A.G. Systematic mapping of genetic interactions in caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nat. Genet. 2006, 38, 896-903.
85. Byrne, A.B.; Weirauch, M.T.; Wong, V.; Koeva, M.; Dixon, S.J.; Stuart, J.M.; Roy, P.J. A global analysis of genetic interactions in caenorhabditis elegans. J. Biol. 2007, 6, 8.
86. Tarailo, M.; Tarailo, S.; Rose, A.M. Synthetic lethal interactions identify phenotypic -interologs{norm of matrix} of the spindle assembly checkpoint components. Genetics 2007, 177, 2525-2530.
87. McLellan, J.; O'Neil, N.; Tarailo, S.; Stoepel, J.; Bryan, J.; Rose, A.; Hieter, P. Synthetic lethal genetic interactions that decrease somatic cell proliferation in caenorhabditis elegans identify the alternative rfc ctf18 as a candidate cancer drug target. Mol. Biol. Cell 2009, 20, 5306-5313.
88. Dixon, S.J.; Fedyshyn, Y.; Koh, J.L.; Prasad, T.S.; Chahwan, C.; Chua, G.; Toufighi, K. Baryshnikova, A.; Hayles, J.; Hoe, K.L., et al. Significant conservation of synthetic lethal genetic interaction networks between distantly related eukaryotes. Proc. Natl. Acad. Sci. USA 2008, 105, 16653-16658.
89. Miyagawa, K.; Tsuruga, T.; Kinomura, A.; Usui, K.; Katsura, M.; Tashiro, S.; Mishima, H. Tanaka, K. A role for rad54b in homologous recombination in human cells. EMBO J. 2002, 21, 175-180.
90. Hiramoto, T.; Nakanishi, T.; Sumiyoshi, T.; Fukuda, T.; Matsuura, S.; Tauchi, H.; Komatsu, K.; Shibasaki, Y.; Inui, H.; Watatani, M., et al. Mutations of a novel human rad54 homologue, rad54b, in primary cancer. Oncogene 1999, 18, 3422-3426.
91. Breitkreutz, B.J.; Stark, C.; Reguly, T.; Boucher, L.; Breitkreutz, A.; Livstone, M.; Oughtred, R.; Lackner, D.H.; Bahler, J.; Wood, V., et al. The biogrid interaction database: 2008 update. Nucleic Acids Res. 2008, 36, D637-D640.
92. Huang, C.H.; Konagaya, A.; Lanza, V.; Sloot, P.M. Introduction to the special section on biogrid: Biomedical computations on the grid. IEEE Trans. Inf. Technol. Biomed. 2008, 12, 133-137.
93. Stark, C.; Breitkreutz, B.J.; Chatr-Aryamontri, A.; Boucher, L.; Oughtred, R.; Livstone, M.S.; Nixon, J.; van Auken, K.; Wang, X.; Shi, X., et al. The biogrid interaction database: 2011 update. Nucleic Acids Res. 2011, 39, D698-D704.
94. Stark, C.; Breitkreutz, B.J.; Reguly, T.; Boucher, L.; Breitkreutz, A.; Tyers, M. Biogrid: A general repository for interaction datasets. Nucleic Acids Res. 2006, 34, D535-D539.
95. Chatr-Aryamontri, A.; Breitkreutz, B.J.; Heinicke, S.; Boucher, L.; Winter, A.; Stark, C.; Nixon, J.; Ramage, L.; Kolas, N.; O'Donnell, L., et al. The biogrid interaction database: 2013 update. Nucleic Acids Res. 2013, 41, D816-D823.
96. Breitkreutz, B.J.; Stark, C.; Tyers, M. Osprey: A network visualization system. Genome Biol. 2003, 4, R22.
97. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003, 13, 2498-2504.
98. Dompe, N.; Rivers, C.S.; Li, L.; Cordes, S.; Schwickart, M.; Punnoose, E.A.; Amler, L. Seshagiri, S.; Tang, J.; Modrusan, Z., et al. A whole-genome rnai screen identifies an 8q22 gene cluster that inhibits death receptor-mediated apoptosis. Proc. Natl. Acad. Sci. USA 2011, 108, E943-E951.
99. Schlabach, M.R.; Luo, J.; Solimini, N.L.; Hu, G.; Xu, Q.; Li, M.Z.; Zhao, Z.; Smogorzewska, A.; Sowa, M.E.; Ang, X.L., et al. Cancer proliferation gene discovery through functional genomics. Science 2008, 319, 620-624.
100. Silva, J.M.; Marran, K.; Parker, J.S.; Silva, J.; Golding, M.; Schlabach, M.R.; Elledge, S.J. Hannon, G.J.; Chang, K. Profiling essential genes in human mammary cells by multiplex rnai screening. Science 2008, 319, 617-620.
101. Xie, L.; Gazin, C.; Park, S.M.; Zhu, L.J.; Debily, M.A.; Kittler, E.L.; Zapp, M.L.; Lapointe, D.; Gobeil, S.; Virbasius, C.M., et al. A synthetic interaction screen identifies factors selectively required for proliferation and tert transcription in p53-deficient human cancer cells. PLoS Genet. 2012, 8, e1003151.
102. Kroll, E.S.; Hyland, K.M.; Hieter, P.; Li, J.J. Establishing genetic interactions by a synthetic dosage lethality phenotype. Genetics 1996, 143, 95-102.
103. Yan, H.; Gibson, S.; Tye, B.K. Mcm2 and mcm3, two proteins important for ars activity, are related in structure and function. Genes Dev. 1991, 5, 944-957.
104. Li, J.J.; Herskowitz, I. Isolation of orc6, a component of the yeast origin recognition complex by a one-hybrid system. Science 1993, 262, 1870-1874.
105. Molenaar, J.J.; Ebus, M.E.; Geerts, D.; Koster, J.; Lamers, F.; Valentijn, L.J.; Westerhout, E.M.; Versteeg, R.; Caron, H.N. Inactivation of CDK2 is synthetically lethal to mycn over-expressing cancer cells. Proc. Natl. Acad. Sci. USA 2009, 106, 12968-12973.
106. Wartiovaara, K.; Barnabe-Heider, F.; Miller, F.D.; Kaplan, D.R. N-myc promotes survival and induces s-phase entry of postmitotic sympathetic neurons. J. Neurosci. 2002, 22, 815-824.
107. Knoepfler, P.S.; Cheng, P.F.; Eisenman, R.N. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev. 2002, 16, 2699-2712.
108. Brodeur, G.M.; Seeger, R.C.; Schwab, M.; Varmus, H.E.; Bishop, J.M. Amplification of n-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 1984, 224, 1121-1124.
109. Garson, J.A.; Pemberton, L.F.; Sheppard, P.W.; Varndell, I.M.; Coakham, H.B.; Kemshead, J.T. N-myc gene expression and oncoprotein characterisation in medulloblastoma. Br. J. Cancer 1989, 59, 889-894.
110. Nisen, P.D.; Zimmerman, K.A.; Cotter, S.V.; Gilbert, F.; Alt, F.W. Enhanced expression of the n-myc gene in wilms' tumors. Cancer Res. 1986, 46, 6217-6222.
111. Schwab, M. Enhanced expression of the cellular oncogene mycn and progression of human neuroblastoma. Adv. Enzyme Regul. 1991, 31, 329-338.
112. Schwab, M. Mycn in neuronal tumours. Cancer Lett. 2004, 204, 179-187.
113. Luo, J.; Emanuele, M.J.; Li, D.; Creighton, C.J.; Schlabach, M.R.; Westbrook, T.F.; Wong, K.K.; Elledge, S.J. A genome-wide rnai screen identifies multiple synthetic lethal interactions with the ras oncogene. Cell 2009, 137, 835-848.
114. Villaruz, L.C.; Socinski, M.A.; Cunningham, D.E.; Chiosea, S.I.; Burns, T.F.; Siegfried, J.M.; Dacic, S. The prognostic and predictive value of kras oncogene substitutions in lung adenocarcinoma. Cancer 2013, 119, 2268-2274.
115. Zhao, S.; Choi, M.; Overton, J.D.; Bellone, S.; Roque, D.M.; Cocco, E.; Guzzo, F.; English, D.P.; Varughese, J.; Gasparrini, S., et al. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma. Proc. Natl. Acad. Sci. USA 2013, 110, 2916-2921.
116. Jenwitheesuk, E.; Horst, J.A.; Rivas, K.L.; van Voorhis, W.C.; Samudrala, R. Novel paradigms for drug discovery: Computational multitarget screening. Trends Pharmacol. Sci. 2008, 29, 62-71.
117. Lopez-Vallejo, F.; Caulfield, T.; Martinez-Mayorga, K.; Giulianotti, M.A.; Nefzi, A.; Houghten, R.A.; Medina-Franco, J.L. Integrating virtual screening and combinatorial chemistry for accelerated drug discovery. Comb. Chem. High Throughput Screen. 2011, 14, 475-487.
118. Guvench, O.; MacKerell, A.D., Jr. Computational evaluation of protein-small molecule binding. Curr. Opin. Struct. Biol. 2009, 19, 56-61.
119. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008, 455, 1061-1068.
120. Furey, T.S. Chip-seq and beyond: New and improved methodologies to detect and characterize protein-DNA interactions. Nat. Rev. Genet. 2012, 13, 840-852.
121. Varley, K.E.; Gertz, J. Bowling, K.M.; Parker, S.L.; Reddy, T.E.; Pauli-Behn, F.; Cross, M.K.; Williams, B.A.; Stamatoyannopoulos, J.A.; Crawford, G.E., et al. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013, 23, 555-567.
122. Robertson, A.G.; Bilenky, M.; Tam, A.; Zhao, Y.; Zeng, T.; Thiessen, N.; Cezard, T.; Fejes, A.P.; Wederell, E.D.; Cullum, R., et al. Genome-wide relationship between histone h3 lysine 4 mono- and tri-methylation and transcription factor binding. Genome Res. 2008, 18, 1906-1917.
123. Neff, T.; Armstrong, S.A. Chromatin maps, histone modifications and leukemia. Leukemia 2009, 23, 1243-1251.