Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Drosophila as a model for chromosomal instability

School of Molecular and Biomedical Science, University of Adelaide, North Terrace, Adelaide S.A. 5006, Australia

Special Issues: Drosophila models of tumourigenesis

Chromosomal instability (CIN) is a common feature of tumours that leads to increased genetic diversity in the tumour and poor clinical outcomes. There is considerable interest in understanding how CIN comes about and how its contribution to drug resistance and metastasis might be counteracted. In the last decade a number of CIN model systems have been developed in Drosophila that offer unique benefits both in understanding the development of CIN in a live animal as well as giving the potential to do genome wide screens for therapeutic candidate genes. This review outlines the mechanisms used in several Drosophila CIN model systems and summarizes some significant outcomes and opportunities that they have produced.
  Article Metrics

Keywords aneuploidy; cell cycle; checkpoint; chromosomal instability; DNA damage; Drosophila; JNK; metabolism; ROS

Citation: Dawei Liu, Zeeshan Shaukat, Rashid Hussain, Mahwish Khan, Stephen L. Gregory. Drosophila as a model for chromosomal instability. AIMS Genetics, 2015, 2(1): 1-12. doi: 10.3934/genet.2015.1.1


  • 1. Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643-649.    
  • 2. Weaver BA, Cleveland DW (2006) Does aneuploidy cause cancer? Curr Opin Cell Biol 18: 658-667.    
  • 3. Rao CV, Yamada HY (2013) Genomic instability and colon carcinogenesis: from the perspective of genes. Front Oncol 3: 130.
  • 4. Duijf PHG, Benezra R (2013) The cancer biology of whole-chromosome instability. Oncogene 32: 4727-4736.    
  • 5. McGranahan N, Burrell RA, Endesfelder D, et al. (2012) Cancer chromosomal instability: therapeutic and diagnostic challenges. EMBO Rep 13: 528-538.    
  • 6. Carter SL, Eklund AC, Kohane IS, et al. (2006) A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 38: 1043-1048.    
  • 7. Bakhoum SF, Swanton C (2014) Chromosomal instability, aneuploidy, and cancer. Front Oncol 4: 161.
  • 8. Roschke A, Kirsch I (2010) Targeting karyotypic complexity and chromosomal instability of cancer cells. Curr Drug Targets 11: 1341-1350.    
  • 9. Roschke AV, Lababidi S, Tonon G, et al. (2005) Karyotypic "state" as a potential determinant for anticancer drug discovery. Proc Natl Acad Sci U S A 102: 2964-2969.    
  • 10. Wallqvist A, Huang R, Covell DG, et al. (2005) Drugs aimed at targeting characteristic karyotypic phenotypes of cancer cells. Mol Cancer Ther 4: 1559-1568.    
  • 11. Shaukat Z, Wong HWS, Nicolson S, et al. (2012) A Screen for Selective Killing of Cells with Chromosomal Instability Induced by a Spindle Checkpoint Defect. PLoS One 7: e47447.    
  • 12. Morais da Silva S, Moutinho-Santos T, Sunkel CE (2013) A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition. J Cell Biol 201: 385-393.    
  • 13. Dekanty A, Barrio L, Muzzopappa M, et al. (2012) Aneuploidy-induced delaminating cells drive tumorigenesis in Drosophila epithelia. Proc Natl Acad Sci U S A 109: 20549-20554.    
  • 14. Silk AD, Zasadil LM, Holland AJ, et al. (2013) Chromosome missegregation rate predicts whether aneuploidy will promote or suppress tumors. Proc Natl Acad Sci U S A 110: E4134-E4141.    
  • 15. Foijer F, DiTommaso T, Donati G, et al. (2013) Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells. Proc Natl Acad Sci U S A 110: 2928-2933.    
  • 16. St Johnston D (2002) The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet 3: 176-188.    
  • 17. Brumby AM, Richardson HE (2005) Using Drosophila melanogaster to map human cancer pathways. Nat Rev Cancer 5: 626-639.    
  • 18. Gonzalez C (2013) Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics. Nat Rev Cancer 13: 172-183.    
  • 19. Tipping M, Perrimon N (2014) Drosophila as a model for context-dependent tumorigenesis. J Cell Physiol 229: 27-33.
  • 20. Gladstone M, Su TT (2011) Chemical genetics and drug screening in Drosophila cancer models. J Genet Genomics 38: 497-504.    
  • 21. Pastor-Pareja JC, Xu T (2013) Dissecting social cell biology and tumors using Drosophila genetics. Annu Rev Genet 47: 51-74.    
  • 22. Castellanos E, Dominguez P, Gonzalez C (2008) Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol 18: 1209-1214.    
  • 23. Basto R, Brunk K, Vinadogrova T, et al. (2008) Centrosome amplification can initiate tumorigenesis in flies. Cell 133: 1032-1042.    
  • 24. Kwon M, Godinho SA, Chandhok NS, et al. (2008) Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 22: 2189-2203.    
  • 25. Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37: 1125-1129.    
  • 26. Poulton JS, Cuningham JC, Peifer M (2014) Acentrosomal Drosophila Epithelial Cells Exhibit Abnormal Cell Division, Leading to Cell Death and Compensatory Proliferation. Dev Cell 30: 731-745.    
  • 27. Jüschke C, Dohnal I, Pichler P, et al. (2013) Transcriptome and proteome quantification of a tumor model provides novel insights into post-transcriptional gene regulation. Genome Biol 14: r133.
  • 28. Purdy A, Su TT (2004) Telomeres: not all breaks are equal. Curr Biol 14: R613-R614.    
  • 29. Krüger A, Ralser M (2011) ATM Is a Redox Sensor Linking Genome Stability and Carbon Metabolism. Sci Signal 4: 4-6.
  • 30. Li TS, Marbán E (2010) Physiological levels of reactive oxygen species are required to maintain genomic stability in stem cells. Stem Cells 28: 1178-1185.
  • 31. Pfau SJ, Amon A (2012) Chromosomal instability and aneuploidy in cancer: from yeast to man. EMBO Rep 13: 515-527.    
  • 32. Albrecht SC, Barata AG, Grosshans J, et al. (2011) In vivo mapping of hydrogen peroxide and oxidized glutathione reveals chemical and regional specificity of redox homeostasis. Cell Metab 14: 819-829.    
  • 33. Dronamraju R, Mason JM (2011) MU2 and HP1a regulate the recognition of double strand breaks in Drosophila melanogaster. PLoS One 6: e25439.
  • 34. Chiolo I, Minoda A, Colmenares SU, et al. (2011) Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell 144: 732-744.    
  • 35. Burrell RA, McClelland SE, Endesfelder D, et al. (2013) Replication stress links structural and numerical cancer chromosomal instability. Nature 494: 492-496.    
  • 36. Bakhoum SF, Silkworth WT, Nardi IK, et al. (2014) The mitotic origin of chromosomal instability. Curr Biol 24: R148-R149.    
  • 37. Liu Y, Nielsen CF, Yao Q, et al. (2014) The origins and processing of ultra fine anaphase DNA bridges. Curr Opin Genet Dev 26C: 1-5.
  • 38. Wong HW, Shaukat Z, Wang J, et al. (2014) JNK signaling is needed to tolerate chromosomal instability. Cell Cycle 13: 622-631.    
  • 39. McNamee LM, Brodsky MH (2009) p53-independent apoptosis limits DNA damage-induced aneuploidy. Genetics 182: 423-435.    
  • 40. Shaukat Z, Liu D, Hussain R, et al. (2014) The Role of JNK Signaling in Responses to Oxidative DNA damage. Curr Drug Targets [in press].
  • 41. Karpac J, Biteau B, Jasper H (2013) Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila. Cell Rep 4: 1250-1261.    
  • 42. Christmann M, Kaina B (2013) Transcriptional regulation of human DNA repair genes following genotoxic stress: trigger mechanisms, inducible responses and genotoxic adaptation. Nucleic Acids Res 41: 8403-8420.    
  • 43. Thompson SL, Compton DA (2008) Examining the link between chromosomal instability and aneuploidy in human cells. J Cell Biol 180: 665-672.    
  • 44. Perez de Castro I, de Carcer G, Malumbres M (2007) A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy. Carcinogenesis 28: 899-912.
  • 45. Hanks S, Coleman K, Reid S, et al. (2004) Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet 36: 1159-1161.    
  • 46. Wood LD, Parsons DW, Jones S, et al. (2007) The genomic landscapes of human breast and colorectal cancers. Science 318: 1108-1113.    
  • 47. Privette LM, Weier JF, Nguyen HN, et al. (2008) Loss of CHFR in human mammary epithelial cells causes genomic instability by disrupting the mitotic spindle assembly checkpoint. Neoplasia 10: 643-652.    
  • 48. Schvartzman JM, Sotillo R, Benezra R (2010) Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer 10: 102-115.    
  • 49. Buffin E, Emre D, Karess RE (2007) Flies without a spindle checkpoint. Nat Cell Biol 9: 565-572.    
  • 50. Shaukat Z, Liu D, Choo A, et al. (2014) Chromosomal instability causes sensitivity to metabolic stress. Oncogene [Epub ahead of print].
  • 51. Rudrapatna VA, Bangi E, Cagan RL (2013) Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion. EMBO Rep 14: 172-177.    
  • 52. Olaharski AJ, Sotelo R, Solorza-Luna G, et al. (2006) Tetraploidy and chromosomal instability are early events during cervical carcinogenesis. Carcinogenesis 27: 337-343.    
  • 53. Margolis RL (2005) Tetraploidy and tumor development. Cancer Cell 8: 353-354.    
  • 54. Galipeau PC, Cowan DS, Sanchez CA, et al. (1996) 17p (p53) allelic losses, 4N (G2/tetraploid) populations, and progression to aneuploidy in Barrett’s esophagus. Proc Natl Acad Sci U S A 93: 7081-7084.    
  • 55. Fujiwara T, Bandi M, Nitta M, et al. (2005) Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 437: 1043-1047.    
  • 56. Ebrahimi S, Gregory SL (2011) Dissecting protein interactions during cytokinesis. Commun Integr Biol 4: 243-244.    
  • 57. D’Avino PP, Savoian MS, Glover DM (2005) Cleavage furrow formation and ingression during animal cytokinesis: a microtubule legacy. J Cell Sci 118: 1549-1558.    
  • 58. Somma MP, Ceprani F, Bucciarelli E, et al. (2008) Identification of Drosophila mitotic genes by combining co-expression analysis and RNA interference. PLoS Genet 4: e1000126.    
  • 59. Eggert US, Mitchison TJ, Field CM (2006) Animal cytokinesis: from parts list to mechanisms. Annu Rev Biochem 75: 543-566.    
  • 60. Fox DT, Duronio RJ (2013) Endoreplication and polyploidy: insights into development and disease. Development 140: 3-12.    
  • 61. Ganem NJ, Cornils H, Chiu SY, et al. (2014) Cytokinesis Failure Triggers Hippo Tumor Suppressor Pathway Activation. Cell 158: 833-848.    
  • 62. Lampson MA, Renduchitala K, Khodjakov A, et al. (2004) Correcting improper chromosome-spindle attachments during cell division. Nat Cell Biol 6: 232-237.
  • 63. Salemi JD, McGilvray PT, Maresca TJ (2013) Development of a Drosophila cell-based error correction assay. Front Oncol 3: 187.
  • 64. Holland AJ, Cleveland DW (2009) Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat Rev Mol Cell Biol 10: 478-487.    
  • 65. Milán M, Clemente-Ruiz M, Dekanty A, et al. (2014) Aneuploidy and tumorigenesis in Drosophila. Semin Cell Dev Biol 28: 110-115.    
  • 66. Marthiens V, Piel M, Basto R (2012) Never tear us apart--the importance of centrosome clustering. J Cell Sci 125: 3281-3292.    
  • 67. Sheltzer JM, Torres EM, Dunham MJ, et al. (2012) Transcriptional consequences of aneuploidy. Proc Natl Acad Sci U S A 109: 12644-12649.    
  • 68. Gorrini C, Harris IS, Mak TW (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12: 931-947.    
  • 69. Oromendia AB, Dodgson SE, Amon A (2012) Aneuploidy causes proteotoxic stress in yeast. Genes Dev 26: 2696-2708.    
  • 70. Lundberg LE, Figueiredo MLA, Stenberg P, et al. (2012) Buffering and proteolysis are induced by segmental monosomy in Drosophila melanogaster. Nucleic Acids Res 40: 5926-5937.    
  • 71. Siegel JJ, Amon A (2012) New insights into the troubles of aneuploidy. Annu Rev Cell Dev Biol 28: 189-214.    
  • 72. Ferrari F, Alekseyenko AA, Park PJ, et al. (2014) Transcriptional control of a whole chromosome: emerging models for dosage compensation. Nat Struct Mol Biol 21: 118-125.    
  • 73. Davidsson J, Veerla S, Johansson B (2013) Constitutional trisomy 8 mosaicism as a model for epigenetic studies of aneuploidy. Epigenetics Chromatin 6: 18.    


This article has been cited by

  • 1. Helena E. Richardson, Drosophila models of cancer, AIMS Genetics, 2015, 2, 1, 97, 10.3934/genet.2015.1.97
  • 2. Rashid Hussain, Zeeshan Shaukat, Mahwish Khan, Robert Saint, Stephen L. Gregory, Phosphoenolpyruvate Carboxykinase Maintains Glycolysis-driven Growth in Drosophila Tumors, Scientific Reports, 2017, 7, 1, 10.1038/s41598-017-11613-2
  • 3. Patrizia Romani, Serena Duchi, Giuseppe Gargiulo, Valeria Cavaliere, Evidence for a novel function of Awd in maintenance of genomic stability, Scientific Reports, 2017, 7, 1, 10.1038/s41598-017-17217-0

Reader Comments

your name: *   your email: *  

Copyright Info: 2015, Stephen L. Gregory, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved