Pan-cancer analysis distinguishes transcriptional changes of aneuploidy from proliferation

Genome Research

Volumn 27, Issue 4, 2017, Pages 501-511

  Buccitelli, Christopher ^a   Salgueiro, Lorena ^b,c   Rowald, Konstantina ^b,c   Sotillo, Rocio ^b,c   Mardin, Balca R ^a,e   Korbel, Jan O ^a,d  

^a EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c Heidelberg Translational Lung Research Center (TLRC)   (Germany)

^d EUROPEAN BIOINFORMATICS INSTITUTE   (United Kingdom)

^e BioMed X Innovation Center   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

MYC PROTEIN; PROTEIN P53; TRANSCRIPTOME; CELL CYCLE PROTEIN;

ACUTE MYELOID LEUKEMIA; ANEUPLOIDY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLADDER CARCINOMA; BREAST CARCINOMA; CANCER PATIENT; CELL GROWTH; CELL PROLIFERATION; CHROMOSOMAL INSTABILITY; CLEAR CELL CARCINOMA; COLORECTAL CARCINOMA; COPY NUMBER VARIATION; ENDOMETRIUM CARCINOMA; GENE EXPRESSION; GENETIC TRANSCRIPTION; GENOMIC INSTABILITY; GLIOBLASTOMA; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; IMMUNOREGULATION; KIDNEY CARCINOMA; LUNG ADENOCARCINOMA; MAJOR CLINICAL STUDY; MALIGNANT NEOPLASM; MOUSE; MULTIPLE CANCER; NONHUMAN; OVARY CARCINOMA; POINT MUTATION; PRIORITY JOURNAL; SOMATIC COPY NUMBER ALTERATION; SQUAMOUS CELL LUNG CARCINOMA; UTERINE CERVIX CARCINOMA; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MUTATION ACCUMULATION; NEOPLASM;

ANEUPLOIDY; CELL CYCLE PROTEINS; CELL PROLIFERATION; DNA COPY NUMBER VARIATIONS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENOMIC INSTABILITY; HUMANS; MUTATION ACCUMULATION; NEOPLASMS; POINT MUTATION; TRANSCRIPTOME;

EID: 85017559196     PISSN: 10889051     EISSN: 15495469     Source Type: Journal    
DOI: 10.1101/gr.212225.116     Document Type: Article

References (79)

1. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, et al. 2013. Signatures of mutational processes in human cancer. Nature 500: 415-421.
2. Bakhoum SF, Silkworth WT, Nardi IK, Nicholson JM, Compton DA, Cimini D. 2014. The mitotic origin of chromosomal instability. Curr Biol 24: R148-R149.
3. Barboza JA, Liu G, Ju Z, El-Naggar AK, Lozano G. 2006. p21 delays tumor onset by preservation of chromosomal stability. Proc Natl Acad Sci 103: 19842-19847.
4. Bieda M, Xu X, Singer MA, Green R, Farnham PJ. 2006. Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome. Genome Res 16: 595-605.
5. Birkbak NJ, Eklund AC, Li Q, McClelland SE, Endesfelder D, Tan P, Tan IB, Richardson AL, Szallasi Z, Swanton C. 2011. Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res 71: 3447-3452.
6. Branzei D, Foiani M. 2010. Maintaining genome stability at the replication fork. Nat Rev Mol Cell Bio 11: 208-219.
7. Burrell RA, McClelland SE, Endesfelder D, Groth P, Weller MC, Shaikh N, Domingo E, Kanu N, Dewhurst SM, Gronroos E, et al. 2013. Replication stress links structural and numerical cancer chromosomal instability. Nature 494: 492-496.
8. The Cancer Genome Atlas Network. 2012. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487: 330-337.
9. The Cancer Genome Atlas Research Network. 2013. Integrated genomic characterization of endometrial carcinoma. Nature 497: 67-73.
10. The Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. 2013. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45: 1113-1120.
11. Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z. 2006. A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 38: 1043-1048.
12. Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE, Premsrirut P, Luo W, Chicas A, Lee CS, et al. 2011. Control of the senescence-Associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. Genes Dev 25: 2125-2136.
13. Ciriello G, Miller ML, Aksoy BA, Senbabaoglu Y, Schultz N, Sander C. 2013. Emerging landscape of oncogenic signatures across human cancers. Nat Genet 45: 1127-1133.
14. Donnelly N, Passerini V, Durrbaum M, Stingele S, Storchova Z. 2014. HSF1 deficiency and impaired HSP90-dependent protein folding are hallmarks of aneuploid human cells. EMBO J 33: 2374-2387.
15. Drake CG, Lipson EJ, Brahmer JR. 2014. Breathing new life into immunotherapy: Review of melanoma, lung and kidney cancer. Nat Rev Clin Oncol 11: 24-37.
16. Durrbaum M, Kuznetsova AY, Passerini V, Stingele S, Stoehr G, Storchova Z. 2014. Unique features of the transcriptional response to model aneuploidy in human cells. BMC Genomics 15: 139.
17. Endesfelder D, Burrell RA, Kanu N, McGranahan N, Howell M, Parker PJ, Downward J, Swanton C, Kschischo M. 2014. Chromosomal instability selects gene copy-number variants encoding core regulators of proliferation in ER+ breast cancer. Cancer Res 74: 4853-4863.
18. Fehrmann RS, Karjalainen JM, Krajewska M, Westra HJ, Maloney D, Simeonov A, Pers TH, Hirschhorn JN, Jansen RC, Schultes EA, et al. 2015. Gene expression analysis identifies global gene dosage sensitivity in cancer. Nat Genet 47: 115-125.
19. Gayther SA, Batley SJ, Linger L, Bannister A, Thorpe K, Chin SF, Daigo Y, Russell P, Wilson A, Sowter HM, et al. 2000. Mutations truncating the EP300 acetylase in human cancers. Nat Genet 24: 300-303.
20. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell 144: 646-674.
21. Helleday T, Eshtad S, Nik-Zainal S. 2014. Mechanisms underlying mutational signatures in human cancers. Nat Rev Genet 15: 585-598.
22. Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, Down T, et al. 2002. The Ensembl genome database project. Nucleic Acids Res 30: 38-41.
23. Janky R, Verfaillie A, Imrichova H, Van de Sande B, Standaert L, Christiaens V, Hulselmans G, Herten K, Naval Sanchez M, Potier D, et al. 2014. iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLoS Comput Biol 10: E1003731.
24. Janssen A, van der Burg M, Szuhai K, Kops GJPL, Medema RH. 2011. Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations. Science 333: 1895-1898.
25. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, et al. 2013. Mutational landscape and significance across 12 major cancer types. Nature 502: 333-339.
26. Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, Lu T, Yankner BA, Campisi J, Elledge SJ. 2015. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 349: Aaa5612.
27. Kim TM, Laird PW, Park PJ. 2013. The landscape of microsatellite instability in colorectal and endometrial cancer genomes. Cell 155: 858-868.
28. Kuznetsova AY, Seget K, Moeller GK, de Pagter MS, de Roos JADM, Durrbaum M, Kuffer C, Muller S, Zaman GJR, Kloosterman WP, et al. 2015. Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. Cell Cycle 14: 2810-2820.
29. Langmead B, Trapnell C, Pop M, Salzberg SL. 2009. Ultrafast and memoryefficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.
30. Laoukili J, Kooistra MR, Bras A, Kauw J, Kerkhoven RM, Morrison A, Clevers H, Medema RH. 2005. FoxM1 is required for execution of the mitotic programme and chromosome stability. Nature Cell Biol 7: 126-136.
31. Laughney AM, Elizalde S, Genovese G, Bakhoum SF. 2015. Dynamics of tumor heterogeneity derived from clonal karyotypic evolution. Cell Rep 12: 809-820.
32. Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G. 2014. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505: 495-501.
33. Lee AJ, Endesfelder D, Rowan AJ, Walther A, Birkbak NJ, Futreal PA, Downward J, Szallasi Z, Tomlinson IP, Howell M, et al. 2011. Chromosomal instability confers intrinsic multidrug resistance. Cancer Res 71: 1858-1870.
34. Liu B, Nicolaides NC, Markowitz S, Willson JK, Parsons RE, Jen J, Papadopolous N, Peltomaki P, de la Chapelle A, Hamilton SR, et al. 1995. Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet 9: 48-55.
35. Love MI, Huber W, Anders S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15: 550.
36. Mellman I, Coukos G, Dranoff G. 2011. Cancer immunotherapy comes of age. Nature 480: 480-489.
37. Mercurio F, Manning AM. 1999. NF-κB as a primary regulator of the stress response. Oncogene 18: 6163-6171.
38. Muzny DM, Bainbridge MN, Chang K, Dinh HH, Drummond JA, Fowler G, Kovar CL, Lewis LR, Morgan MB, Newsham IF, et al. 2012.Comprehensive molecular characterization of human colon and rectal cancer. Nature 487: 330-337.
39. Nam HJ, van Deursen JM. 2014. Cyclin B2 and p53 control proper timing of centrosome separation. Nat Cell Biol 16: 538-549.
40. Negrini S, Gorgoulis VG, Halazonetis TD. 2010. Genomic instability-An evolving hallmark of cancer. Nat Rev Mol Cell Biol 11: 220-228.
41. Neumann B, Walter T, Heriche JK, Bulkescher J, Erfle H, Conrad C, Rogers P, Poser I, Held M, Liebel U, et al. 2010. Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Nature 464: 721-727.
42. Oromendia AB, Dodgson SE, Amon A. 2012. Aneuploidy causes proteotoxic stress in yeast. Genes Dev 26: 2696-2708.
43. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Guarino E, Salguero I, et al. 2013. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 45: 136-144.
44. Parikh N, Hilsenbeck S, Creighton CJ, Dayaram T, Shuck R, Shinbrot E, Xi L, Gibbs RA, Wheeler DA, Donehower LA. 2014. Effects of TP53 mutational status on gene expression patterns across 10 human cancer types. J Pathol 232: 522-533.
45. Passerini V, Ozeri-Galai E, de Pagter MS, Donnelly N, Schmalbrock S, Kloosterman WP, Kerem B, Storchova Z. 2016. The presence of extra chromosomes leads to genomic instability. Nat Commun 7: 10754.
46. Piret B, Schoonbroodt S, Piette J. 1999. The ATM protein is required for sustained activation of NF-κB following DNA damage. Oncogene 18: 2261-2271.
47. R Core Team. 2008. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.Rproject.org/.
48. Rancati G, Pavelka N, Fleharty B, Noll A, Trimble R, Walton K, Perera A, Staehling-Hampton K, Seidel CW, Li R. 2008. Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. Cell 135: 879-893.
49. Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA, Dynlacht BD. 2002. E2F integrates cell cycle progression with DNA repair, replication, and G2/M checkpoints. Genes Dev 16: 245-256.
50. Rowald K, Mantovan M, Passos J, Buccitelli C, Mardin BR, Korbel JO, Jechlinger M, Sotillo R. 2016. Negative selection and chromosome instability induced by Mad2 overexpression delay breast cancer but facilitate oncogene independent outgrowth. Cell Rep 15: 2679-2691.
51. Sadasivam S, DeCaprio JA. 2013. The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nat Rev Cancer 13: 585-595.
52. Santagata S, Mendillo ML, Tang YC, Subramanian A, Perley CC, Roche SP, Wong B, Narayan R, Kwon H, Koeva M, et al. 2013. Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science 341: 1238303.
53. Santaguida S, Amon A. 2015. Short-And long-Term effects of chromosome mis-segregation and aneuploidy. Nat Rev Mol Cell Biol 16: 473-485.
54. Santaguida S, Vasile E, White E, Amon A. 2015. Aneuploidy-induced cellular stresses limit autophagic degradation. Genes Dev 29: 2010-2021.
55. Schvartzman JM, Sotillo R, Benezra R. 2010. Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer 10: 102-115.
56. Schvartzman JM, Duijf PH, Sotillo R, Coker C, Benezra R. 2011. Mad2 is a critical mediator of the chromosome instability observed upon Rb and p53 pathway inhibition. Cancer Cell 19: 701-714.
57. Selmecki A, Forche A, Berman J. 2006. Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313: 367-370.
58. Selmecki AM, Maruvka YE, Richmond PA, Guillet M, Shoresh N, Sorenson AL, De S, Kishony R, Michor F, Dowell R, et al. 2015. Polyploidy can drive rapid adaptation in yeast. Nature 519: 349-352.
59. Senovilla L, Vitale I, Martins I, TaillerM, Pailleret C, Michaud M, Galluzzi L, Adjemian S, Kepp O, Niso-Santano M, et al. 2012. An immunosurveillance mechanism controls cancer cell ploidy. Science 337: 1678-1684.
60. Settembre C, Ballabio A. 2011. TFEB regulates autophagy: An integrated coordination of cellular degradation and recycling processes. Autophagy 7: 1379-1381.
61. Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, et al. 2011. TFEB links autophagy to lysosomal biogenesis. Science 332: 1429-1433.
62. Sheltzer JM. 2013. A transcriptional and metabolic signature of primary aneuploidy is present in chromosomally unstable cancer cells and informs clinical prognosis. Cancer Res 73: 6401-6412.
63. Sheltzer JM, Blank HM, Pfau SJ, Tange Y, George BM, Humpton TJ, Brito IL, Hiraoka Y, Niwa O, Amon A. 2011. Aneuploidy drives genomic instability in yeast. Science 333: 1026-1030.
64. Sheltzer JM, Torres EM, Dunham MJ, Amon A. 2012. Transcriptional consequences of aneuploidy. Proc Natl Acad Sci 109: 12644-12649.
65. Sheltzer JM, Ko JH, Replogle JM, Habibe Burgos NC, Chung ES, Meehl CM, Sayles NM, Passerini V, Storchova Z, Amon A. 2016. Single-chromosome gains commonly function as tumor suppressors. Cancer Cell 31: 240-255.
66. Shlien A, Campbell BB, de Borja R, Alexandrov LB, Merico D, Wedge D, Van Loo P, Tarpey PS, Coupland P, Behjati S, et al. 2015. Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Nat Genet 47: 257-262.
67. Silk AD, Zasadil LM, Holland AJ, Vitre B, Cleveland DW, Weaver BA. 2013. Chromosome missegregation rate predicts whether aneuploidy will promote or suppress tumors. Proc Natl Acad Sci 110: E4134-E4141.
68. Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordon-Cardo C, Lowe SW, Benezra R. 2007. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11: 9-23.
69. Sotillo R, Schvartzman JM, Socci ND, Benezra R. 2010. Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. Nature 464: 436-440.
70. Stingele S, Stoehr G, Peplowska K, Cox J, Mann M, Storchova Z. 2012. Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells. Mol Syst Biol 8: 608.
71. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. 2005. Gene set enrichment analysis: A knowledge-based approach for interpreting genome- wide expression profiles. Proc Natl Acad Sci 102: 15545-15550.
72. Tang YC, Williams BR, Siegel JJ, Amon A. 2011. Identification of aneuploidy- selective antiproliferation compounds. Cell 144: 499-512.
73. Thompson SL, Compton DA. 2010. Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J Cell Biol 188: 369-381.
74. Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ, Amon A. 2007. Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317: 916-924.
75. Torres EM, Dephoure N, Panneerselvam A, Tucker CM, Whittaker CA, Gygi SP, Dunham MJ, Amon A. 2010. Identification of aneuploidy-Tolerating mutations. Cell 143: 71-83.
76. Voce DJ, Schmitt AM, Uppal A, McNerney ME, Bernal GM, Cahill KE, Wahlstrom JS, Nassiri A, Yu X, Crawley CD, et al. 2015. Nfkb1 is a haploinsufficient DNA damage-specific tumor suppressor. Oncogene 34: 2807-2813.
77. Williams BR, Prabhu VR, Hunter KE, Glazier CM, Whittaker CA, Housman DE, Amon A. 2008. Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science 322: 703-709.
78. Yang L, Luquette LJ, Gehlenborg N, Xi R, Haseley PS, Hsieh CH, Zhang C, Ren X, Protopopov A, Chin L, et al. 2013. Diverse mechanisms of somatic structural variations in human cancer genomes. Cell 153: 919-929.
79. Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhang CZ, Wala J, Mermel CH, et al. 2013. Pan-cancer patterns of somatic copy number alteration. Nat Genet 45: 1134-1140.