Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity

Cancer Research

Volumn 74, Issue 1, 2014, Pages 287-297

  Bajrami, Ilirjana ^a   Frankum, Jessica R ^a   Konde, Asha ^a   Miller, Rowan E ^a   Rehman, Farah L ^a   Brough, Rachel ^a   Campbell, James ^a,c   Sims, David ^a   Rafiq, Rumana ^a   Hooper, Sean ^a   Chen, Lina ^c   Kozarewa, Iwanka ^c   Assiotis, Ioannis ^c   Fenwick, Kerry ^c   Natrajan, Rachael ^b   Lord, Christopher J ^a,c   Ashworth, Alan ^a,c  

^a CRUK Gene Function Laboratory   (United Kingdom)

^b Breakthrough Breast Cancer Research Centre   (United Kingdom)

^c INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 2; OLAPARIB; PROTEIN CDK12; REGULATOR PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CDK12 GENE; CHROMATIN ASSEMBLY AND DISASSEMBLY; CONTROLLED STUDY; DNA BINDING; DNA COHESION; DNA REPAIR; DNA SEQUENCE; DRUG SENSITIVITY; ENZYME INHIBITION; GENE EXPRESSION; GENE IDENTIFICATION; GENETIC ASSOCIATION; GENETIC RECOMBINATION; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; LETHAL GENE; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; PRIORITY JOURNAL; SENSITIVITY ANALYSIS; TUMOR CELL LINE; TUMOR SUPPRESSOR GENE;

ANIMALS; CYCLIN-DEPENDENT KINASES; CYSTADENOCARCINOMA, SEROUS; ENZYME INHIBITORS; FEMALE; GENE EXPRESSION PROFILING; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; GERM-LINE MUTATION; HUMANS; IMMUNOHISTOCHEMISTRY; MICE; MICE, NUDE; OVARIAN NEOPLASMS; PHTHALAZINES; PIPERAZINES; POLY(ADP-RIBOSE) POLYMERASES; RANDOM ALLOCATION; RNA, SMALL INTERFERING; SURVIVAL ANALYSIS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84892712017     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-2541     Document Type: Article

References (41)

1. De Vos M, Schreiber V, Dantzer F. The diverse roles and clinical relevance of PARPs in DNA damage repair: current state of the art. Biochem Pharmacol 2012;84:137-46.
2. Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature 2012;481:287-94.
3. Ledermann J, Philipp H, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer (SOC) and aBRCA mutation (BRCAm). J Clin Oncol 31, 2013 (suppl; abstr 5505).
4. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012;366:1382-92.
5. McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res 2006;66:8109-15.
6. Turner NC, Lord CJ, Iorns E, Brough R, Swift S, Elliott R, et al. A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor. EMBO J 2008;27:1368-77.
7. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005;434:917-21.
8. Mendes-Pereira AM, Martin SA, Brough R, McCarthy A, Taylor JR, Kim JS, et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med 2009;1:315-22.
9. Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 2008;451:1111-5.
10. Brough R, Bajrami I, Vatcheva R, Natrajan R, Reis-Filho JS, Lord CJ, et al. APRIN is a cell cycle specific BRCA2-interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer. EMBO J 2012;31:1160-76.
11. Saeki H, Siaud N, Christ N, Wiegant WW, van Buul PP, Han M, et al. Suppression of the DNA repair defects of BRCA2-deficient cells with heterologous protein fusions. Proc Natl Acad Sci U S A 2006;103: 8768-73.
12. Pierce AJ, Johnson RD, Thompson LH, Jasin M. XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes Dev 1999;13:2633-8.
13. TCGA. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609-15.
14. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012;2: 401-4.
15. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013;6:pl1.
16. Lee KY, Yang K, Cohn MA, Sikdar N, D'Andrea AD, Myung K. Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear antigen (PCNA) through Its interactions with PCNA and USP1. J Biol Chem 2010;285:10362-9.
17. Sikdar N, Banerjee S, Lee KY, Wincovitch S, Pak E, Nakanishi K, et al. DNA damage responses by human ELG1 in S phase are important to maintain genomic integrity. Cell Cycle 2009;8:3199-207.
18. Bell DW, Sikdar N, Lee KY, Price JC, Chatterjee R, Park HD, et al. Predisposition to cancer caused by genetic and functional defects of mammalian Atad5. PLoS Genet 2011;7:e1002245.
19. Mendes-Pereira AM, Sims D, Dexter T, Fenwick K, Assiotis I, Kozarewa I, et al. Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen. Proc Natl Acad Sci U S A 2012;109:2730-5.
20. Sims D, Mendes-Pereira AM, Frankum J, Burgess D, Cerone MA, Lombardelli C, et al. High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing. Genome Biol 2011;12:R104.
21. Bassik MC, Lebbink RJ, Churchman LS, Ingolia NT, Patena W, LeProust EM, et al. Rapid creation and quantitative monitoring of high coverage shRNA libraries. Nat Methods 2009;6:443-5.
22. Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 2011;43:879-82.
23. Lord CJ, McDonald S, Swift S, Turner NC, Ashworth A. A highthroughput RNA interference screen for DNA repair determinants of PARP inhibitor sensitivity. DNA Repair (Amst) 2008;7:2010-9.
24. Min A, Im SA, Yoon YK, Song SH, Nam HJ, Hur HS, et al. RAD51Cdeficient cancer cells are highly sensitive to the PARP inhibitor olaparib. Mol Cancer Ther 2013;12:865-77.
25. Murai J, Yang K, Dejsuphong D, Hirota K, Takeda S, D'Andrea AD. The USP1/UAF1 complex promotes double-strand break repair through homologous recombination. Mol Cell Biol 2011;31:2462-9.
26. Wu N, Yu H. TheSmccomplexes in DNAdamage response. Cell Biosci 2012;2:5.
27. Horton JK, Wilson SH. Predicting enhanced cell killing through PARP inhibition. Mol Cancer Res 2013;11:13-8.
28. Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of PARP1 and PARP2 by clinicalPARP inhibitors. Cancer Res 2012;72:5588-99.
29. Pettitt SJ, Rehman FL, Bajrami I, Brough R, Wallberg F, Kozarewa I, et al. A genetic screen using the PiggyBac transposon in haploid cells identifies Parp1 as a mediator of olaparib toxicity. PLoS One 2013;8: e61520.
30. TCGA [cited 2013 Jul 20]. Available from: https://tcga-data.nci.nih.gov/ tcga/.
31. COSMIC [cited 2013 Jul 20]. Available from: http://www.sanger.ac.uk/ genetics/CGP/cosmic/.
32. ICGC [cited 2013 Jul 20]. Available from: http://icgc.org/.
33. Carter SL, Cibulskis K, Helman E, McKenna A, Shen H, Zack T, et al. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol 2012;30:413-21.
34. Sakai W, Swisher EM, Jacquemont C, Chandramohan KV, Couch FJ, Langdon SP, et al. Functional restoration of BRCA2 protein by secondary BRCA2 mutations in BRCA2-mutated ovarian carcinoma. Cancer Res 2009;69:6381-6.
35. CCLE [cited 2013 Jul 20]. Available from: http://www.broadinstitute.org/ ccle/home.
36. Blazek D, Kohoutek J, Bartholomeeusen K, Johansen E, Hulinkova P, Luo Z, et al. The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev 2011;25:2158-72.
37. Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, et al. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 2010;141:243-54.
38. Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol 2010;17:688-95.
39. Jaspers JE, Kersbergen A, Boon U, Sol W, van Deemter L, Zander SA, et al. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov 2013;3:68-81.
40. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol 2011;12:852-61.
41. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRINGv9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013;41:D808-15.