Cancer chromosomal instability: Therapeutic and diagnostic challenges

EMBO Reports

Volumn 13, Issue 6, 2012, Pages 528-538

  McGranahan, Nicholas ^a,b   Burrell, Rebecca A ^a   Endesfelder, David ^a,c   Novelli, Marco R ^b   Swanton, Charles ^a,b  

^a CRUK London Research Institute   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF APPLIED SCIENCES   (Germany)

Author keywords

aneuploidy; cancer; chromosomal instability; genomic instability; intra tumour heterogeneity

Indexed keywords

AURORA A KINASE; AURORA B KINASE; CELL CYCLE PROTEIN 20; CYCLIN B1; CYCLIN B2; DNA; ESTROGEN RECEPTOR; FLUOROURACIL; HISTONE H2AX;

ADJUVANT THERAPY; ANEUPLOIDY; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER CELL; CANCER GRADING; CANCER PATIENT; CANCER PROGNOSIS; CANCER STAGING; CELL CYCLE; CELL POPULATION; CHROMOSOMAL INSTABILITY; CHROMOSOME LOSS; CLINICAL ASSESSMENT; COLON CANCER; COLORECTAL CARCINOMA; CYTOMETRY; DISEASE ASSOCIATION; DISEASE CLASSIFICATION; DNA REPAIR; ENDOMETRIUM CANCER; FLUORESCENCE IN SITU HYBRIDIZATION; HUMAN; IN VIVO STUDY; LARGE CELL LYMPHOMA; LUNG NON SMALL CELL CANCER; LYMPH NODE METASTASIS; META ANALYSIS; MITOSIS SPINDLE; MOUTH SQUAMOUS CELL CARCINOMA; MYELODYSPLASTIC SYNDROME; NEOPLASM; OVARY CANCER; PANCREAS CARCINOMA; PANCREAS ISLET CELL TUMOR; PRIORITY JOURNAL; RETROSPECTIVE STUDY; REVIEW; RISK ASSESSMENT; SARCOMA; SYNOVIAL SARCOMA; TELOMERE;

ANIMALS; CHROMOSOMAL INSTABILITY; CHROMOSOME SEGREGATION; HUMANS; KARYOTYPING; MOLECULAR DIAGNOSTIC TECHNIQUES; MOLECULAR TARGETED THERAPY; NEOPLASMS;

EID: 84861851519     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.1038/embor.2012.61     Document Type: Review

References (103)

1. Negrini S, Gorgoulis VG, Halazonetis TD (2010) Genomic instability - an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11: 220-228
2. Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643-649 (Pubitemid 29003936)
3. Geigl JB, Obenauf AC, Schwarzbraun T, Speicher MR (2008) Defining 'chromosomal instability'. Trends Genet 24: 64-69
4. Choi CM, Seo KW, Jang SJ, Oh YM, Shim TS, Kim WS, Lee DS, Lee SD (2009) 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 64: 66-70
5. 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 (Pubitemid 44325930)
6. Walther A, Houlston R, Tomlinson I (2008) Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut 57: 941-950 (Pubitemid 351919529)
7. Gerlinger M, Swanton C (2010) How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine. Br J Cancer 103: 1139-1143
8. Lee AJ et al (2011) Chromosomal instability confers intrinsic multidrug resistance. Cancer Res 71: 1858-1870
9. Habermann JK et al (2009) The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome. Int J Cancer 124: 1552-1564
10. Gordon DJ, Resio B, Pellman D (2012) Causes and consequences of aneuploidy in cancer. Nat Rev Genet 13: 189-203
11. Gollin SM (2005) Mechanisms leading to chromosomal instability. Semin Cancer Biol 15: 33-42
12. Beroukhim R et al (2010) The landscape of somatic copy-number alteration across human cancers. Nature 463: 899-905
13. Weaver BAA, Silk AD, Montagna C, Verdier-Pinard P, Cleveland DW (2007) Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell 11: 25-36 (Pubitemid 46070223)
14. Paulsson K, Johansson B (2009) High hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 48: 637-660
15. Kaneko Y, Knudson AG (2000) Mechanism and relevance of ploidy in neuroblastoma. Genes Chromosomes Cancer 29: 89-95
16. Thompson SL, Compton DA (2008) Examining the link between chromosomal instability and aneuploidy in human cells. J Cell Biol 180: 665-672 (Pubitemid 351397764)
17. Lengauer C, Kinzler KW, Vogelstein B (1997) Genetic instability in colorectal cancers. Nature 386: 623-627 (Pubitemid 27175430)
18. Holland AJ, Cleveland DW (2009) Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat Rev Mol Cell Biol 10: 478-487
19. Hanks S et al (2004) Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet 36: 1159-1161 (Pubitemid 41288963)
20. Grabsch H, Takeno S, Parsons WJ, Pomjanski N, Boecking A, Gabbert HE, Mueller W (2003) Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer - association with tumour cell proliferation. J Pathol 200: 16-22 (Pubitemid 36592631)
21. Wang XH, Jin DY, Ng RWM, Feng HC, Wong YC, Cheung ALM, Tsao SW (2002) Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells. Cancer Res 62: 1662-1668 (Pubitemid 34408486)
22. Barber TD et al (2008) Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc Natl Acad Sci USA 105: 3443-3448
23. Zhang NG et al (2008) Overexpression of Separase induces aneuploidy and mammary tumorigenesis. Proc Natl Acad Sci USA 105: 13033-13038
24. Meyer R, Fofanov V, Panigrahi A, Merchant F, Zhang NG, Pati D (2009) Overexpression and mislocalization of the chromosomal segregation protein separase in multiple human cancers. Clin Cancer Res 15: 2703-2710
25. Iwaizumi M et al (2009) Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer. Gut 58: 249-260
26. Ganem NJ, Godinho SA, Pellman D (2009) A mechanism linking extra centrosomes to chromosomal instability. Nature 460: 278-282
27. Gregan J, Polakova S, Zhang LJ, Tolic-Norrelykke IM, Cimini D (2011) Merotelic kinetochore attachment: causes and effects. Trends Cell Biol 21: 374-381
28. Carmena M, Ruchaud S, Earnshaw WC (2009) Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins. Curr Opin Cell Biol 21: 796-805
29. Janssen A, van der Burg M, Szuhai K, Kops GJ, Medema RH (2011) Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations. Science 333: 1895-1898
30. Crasta K et al (2012) DNA breaks and chromosome pulverization from errors in mitosis. Nature 482: 53-58
31. Bayani J, Selvarajah S, Maire G, Vukovic B, Al-Romaih K, Zielenska M, Squire JA (2007) Genomic mechanisms and measurement of structural and numerical instability in cancer cells. Semin Cancer Biol 17: 5-18 (Pubitemid 46084849)
32. Jones RN (2005) McClintock's controlling elements: the full story. Cytogenet Genome Res 109: 90-103
33. Gisselsson D et al (2000) Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity. Proc Natl Acad Sci USA 97: 5357-5362 (Pubitemid 30313723)
34. Stewenius Y, Gorunova L, Jonson T, Larsson N, Hoglund M, Mandahl N, Mertens F, Mitelman F, Gisselsson D (2005) Structural and numerical chromosome changes in colon cancer develop through telomere-mediated anaphase bridges, not through mitotic multipolarity. Proc Natl Acad Sci USA 102: 5541-5546 (Pubitemid 40530294)
35. Pampalona J, Soler D, Genescà A, Tusell L (2010) Whole chromosome loss is promoted by telomere dysfunction in primary cells. Genes Chromosomes Cancer 49: 368-378
36. Feldser DM, Hackett JA, Greider CW (2003) Telomere dysfunction and the initiation of genome instability. Nat Rev Cancer 3: 623-627 (Pubitemid 37328834)
37. Perera SA et al (2008) Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer. Carcinogenesis 29: 747-753 (Pubitemid 351494161)
38. Bailey SM, Murnane JP (2006) Telomeres, chromosome instability and cancer. Nucleic Acids Res 34: 2408-2417 (Pubitemid 43985678)
39. Ozeri-Galai E, Lebofsky R, Rahat A, Bester AC, Bensimon A, Kerem B (2011) Failure of origin activation in response to fork stalling leads to chromosomal instability at fragile sites. Mol Cell 43: 122-131
40. Dereli-Öz A, Versini G, Halazonetis TD (2011) Studies of genomic copy number changes in human cancers reveal signatures of DNA replication stress. Mol Oncol 5: 308-314
41. Mills KD, Ferguson DO, Alt FW (2003) The role of DNA breaks in genomic instability and tumorigenesis. Immunol Rev 194: 77-95 (Pubitemid 36886430)
42. Boland CR, Komarova NL, Goel A (2009) Chromosomal instability and cancer: not just one CINgle mechanism. Gut 58: 163-164
43. McClelland SE, Burrell RA, Swanton C (2009) Chromosomal instability: a composite phenotype that influences sensitivity to chemotherapy. Cell Cycle 8: 3262-3266
44. Roschke AV, Tonon G, Gehlhaus KS, McTyre N, Bussey KJ, Lababidi S, Scudiero DA, Weinstein JN, Kirsch IR (2003) Karyotypic complexity of the NCI-60 drug-screening panel. Cancer Res 63: 8634-8647 (Pubitemid 38064038)
45. Martinez C, van Wely KHM (2010) Are aneuploidy and chromosome breakage caused by a CINgle mechanism? Cell Cycle 9: 2275-2280
46. Smid M, Hoes M, Sieuwerts AM, Sleijfer S, Zhang Y, Wang Y, Foekens JA, Martens JWM (2011) Patterns and incidence of chromosomal instability and their prognostic relevance in breast cancer subtypes. Breast Cancer Res Treat 128: 23-30
47. Endesfelder D, McGranahan N, Birkbak NJ, Szallasi Z, Kschischo M, Graham TA, Swanton C (2011) A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables. Oncotarget 2: 529-537
48. Bakhoum SF, Danilova OV, Kaur P, Levy NB, Compton DA (2011) Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma. Clin Cancer Res 17: 7704-7711
49. Speicher MR, Carter NP (2005) The new cytogenetics: Blurring the boundaries with molecular biology. Nat Rev Genet 6: 782-792 (Pubitemid 41400836)
50. Takami S, Kawasome C, Kinoshita M, Koyama H, Noguchi S (2001) Chromosomal instability detected by fluorescence in situ hybridization in Japanese breast cancer patients. Clin Chim Acta 308: 127-131 (Pubitemid 32537617)
51. Yoo JW, Seo KW, Jang SJ, Oh YM, Shim TS, Kim WS, Lee DS, Lee SD, Choi CM (2010) 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 25: 863-867
52. Nakamura H, Saji H, Idiris A, Kawasaki N, Hosaka M, Ogata A, Saijo T, Kato H (2003) 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 9: 2294-2299 (Pubitemid 36687655)
53. Sato H, Uzawa N, Takahashi KI, Myo K, Ohyama Y, Amagasa T (2010) Prognostic utility of chromosomal instability detected by fluorescence in situ hybridization in fine-needle aspirates from oral squamous cell carcinomas. BMC Cancer 10: 182
54. Darzynkiewicz Z, Halicka HD, Zhao H (2010) Analysis of cellular DNA content by flow and laser scanning cytometry. Adv Exp Med Biol 676: 137-147
55. Kronenwett U et al (2004) Improved grading of breast adenocarcinomas based on genomic instability. Cancer Res 64: 904-909 (Pubitemid 38176891)
56. Fiegler H, Geigl JB, Langer S, Rigler D, Porter K, Unger K, Carter NP, Speicher MR (2007) High resolution array-CGH analysis of single cells. Nucleic Acids Res 35: e15
57. Navin N et al (2011) Tumour evolution inferred by single-cell sequencing. Nature 472: 90-94
58. Pinkel D, Albertson DG (2005) Array comparative genomic hybridization and its applications in cancer. Nat Genet 37: S11-S17 (Pubitemid 40770398)
59. Stephens PJ et al (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144: 27-40
60. Chin SF et al (2007) High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer. Genome Biol 8: R215
61. Birkbak NJ et al (2011) Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res 71: 3447-3452
62. Stephens PJ et al (2009) Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 462: 1005-1010
63. Maley CC et al (2006) Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet 38: 468-473
64. Gerlinger M et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883-892
65. Whitfield ML et al (2002) Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell 13: 1977-2000 (Pubitemid 34651487)
66. Mettu RK, Wan YW, Habermann JK, Ried T, Guo NL (2010) A 12-gene genomic instability signature predicts clinical outcomes in multiple cancer types. Int J Biol Markers 25: 219-228
67. Schvartzman JM, Sotillo R, Benezra R (2010) Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer 10: 102-115
68. Baker DJ, Jin F, Jeganathan KB, van Deursen JM (2009) Whole chromosome instability caused by Bub1 insufficiency drives tumorigenesis through tumor suppressor gene loss of heterozygosity. Cancer Cell 16: 475-486
69. Roylance R et al (2011) Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol Biomarkers Prev 20: 2183-2194
70. Murayama-Hosokawa S et al (2010) 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 29: 1897-1908
71. Nakagawa Y, Numoto K, Yoshida A, Kunisada T, Ohata H, Takeda K, Wai D, Poremba C, Ozaki T (2006) Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization. J Cancer Res Clin Oncol 132: 444-450
72. Cahill DP, Kinzler KW, Vogelstein B, Lengauer C (1999) Genetic instability and darwinian selection in tumours. Trends Biochem Sci 24: M57-M60
73. 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
74. Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, Florens L, Sanderson BW, Hattem GL, Li R (2010) Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468: 321-325
75. Komarova N (2004) Does cancer solve an optimization problem? Cell Cycle 3: 840-844
76. Swanton C et al (2009) Chromosomal instability determines taxane response. Proc Natl Acad Sci USA 106: 8671-8676
77. Duesberg P, Stindl R, Hehlmann R (2000) Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy. Proc Natl Acad Sci USA 97: 14295-14300 (Pubitemid 32036702)
78. Li R, Hehlman R, Sachs R, Duesberg P (2005) Chromosomal alterations cause the high rates and wide ranges of drug resistance in cancer cells. Cancer Genet Cytogenet 163: 44-56 (Pubitemid 41597009)
79. Jonkers YMH et al (2005) Chromosomal instability predicts metastatic disease in patients with insulinomas. Endocr Relat Cancer 12: 435-447 (Pubitemid 40896457)
80. 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 (Pubitemid 47301313)
81. 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
82. Ozery-Flato M, Linhart C, Trakhtenbrot L, Izraeli S, Shamir R (2011) Large-scale analysis of chromosomal aberrations in cancer karyotypes reveals two distinct paths to aneuploidy. Genome Biol 12: R61
83. Loeb LA (2001) A mutator phenotype in cancer. Cancer Res 61: 3230-3239
84. Komarova NL, Wodarz D (2004) The optimal rate of chromosome loss for the inactivation of tumor suppressor genes in cancer. Proc Natl Acad Sci USA 101: 7017-7021 (Pubitemid 38596435)
85. Lynch M, Bürger R, Butcher D, Gabriel W (1993) The mutational meltdown in asexual populations. J Hered 84: 339-344 (Pubitemid 23312694)
86. Eigen M (2002) Error catastrophe and antiviral strategy. Proc Natl Acad Sci USA 99: 13374-13376
87. Kops G, Foltz DR, Cleveland DW (2004) Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint. Proc Natl Acad Sci USA 101: 8699-8704 (Pubitemid 38745834)
88. Roylance R et al (2011) Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol Biomarkers Prev 20: 2183-2184
89. Swanton C, Burrell RA, Futreal PA (2011) Breast cancer genome heterogeneity: a challenge to personalised medicine? Breast Cancer Res 13: 104
90. da Costa LT, Lengauer H (2002) Exploring and exploiting instability. Cancer Biol Ther 1: 212-225
91. Roschke AV, Kirsch IR (2005) Targeting cancer cells by exploiting karyotypic complexity and chromosomal instability. Cell Cycle 4: 679-682 (Pubitemid 41353851)
92. Burrell RA, Juul N, Johnston SR, Reis JS, Szallasi Z, Swanton C (2010) Targeting chromosomal instability and tumour heterogeneity in HER2-positive breast cancer. J Cell Biochem 111: 782-790
93. Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M, Pellman D (2008) Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 22: 2189-2203
94. Janssen A, Kops G, Medema RH (2009) Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells. Proc Natl Acad Sci USA 106: 19108-19113
95. 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
96. Storchová Z, Breneman A, Cande J, Dunn J, Burbank K, O'Toole E, Pellman D (2006) Genome-wide genetic analysis of polyploidy in yeast. Nature 443: 541-547 (Pubitemid 44527285)
97. Thompson SL, Compton DA (2010) Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J Cell Biol 188: 369-381
98. Roschke AV, Kirsch IR (2010) Targeting karyotypic complexity and chromosomal instability of cancer cells. Current Drug Targets 11: 1341-1350
99. Tang YC, Williams BR, Siegel JJ, Amon A (2011) Identification of aneuploidy-selective antiproliferation compounds. Cell 144: 499-512
100. Chen G, Bradford WD, Seidel CW, Li R (2012) Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. Nature 482: 246-250
101. Manchado E, Malumbres M (2011) Targeting aneuploidy for cancer therapy. Cell 144: 465-466
102. Heilig CE, Loffler H, Mahlknecht U, Janssen JWG, Ho AD, Jauch A, Kramer A (2010) Chromosomal instability correlates with poor outcome in patients with myelodysplastic syndromes irrespectively of the cytogenetic risk group. J Cell Mol Med 14: 895-902
103. Bergshoeff VE, Hopman AHN, Zwijnenberg IR, Ramaekers FCS, Bot FJ, Kremer B, Manni JJ, Speel EJM (2008) Chromosome instability in resection margins predicts recurrence of oral squamous cell carcinoma. J Pathol 215: 347-348 (Pubitemid 351956716)