1932

Abstract

Chromosomal rearrangements are generally thought to accumulate gradually over many generations. However, DNA sequencing of cancer and congenital disorders uncovered a new pattern in which multiple rearrangements arise all at once. The most striking example, chromothripsis, is characterized by tens or hundreds of rearrangements confined to a single chromosome or to local regions over a few chromosomes. Genomic analysis of chromothripsis and the search for its biological mechanism have led to new insights on how chromosome segregation errors can generate mutagenesis and changes to the karyotype. Here, we review the genomic features of chromothripsis and summarize recent progress on understanding its mechanism. This includes reviewing new work indicating that one mechanism to generate chromothripsis is through the physical isolation of chromosomes in abnormal nuclear structures (micronuclei). We also discuss connections revealed by recent genomic analysis of cancers between chromothripsis, chromosome bridges, and ring chromosomes.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-120213-092228
2015-11-23
2024-06-14
Loading full text...

Full text loading...

/deliver/fulltext/genet/49/1/annurev-genet-120213-092228.html?itemId=/content/journals/10.1146/annurev-genet-120213-092228&mimeType=html&fmt=ahah

Literature Cited

  1. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S. 1.  et al. 2013. Signatures of mutational processes in human cancer. Nature 500:415–21 [Google Scholar]
  2. Alt FW, Kellems RE, Bertino JR, Schimke RT. 2.  1978. Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells. J. Biol. Chem. 253:1357–70 [Google Scholar]
  3. Bailey JA, Baertsch R, Kent WJ, Haussler D, Eichler EE. 3.  2004. Hotspots of mammalian chromosomal evolution. Genome Biol. 5:R23 [Google Scholar]
  4. Barrick JE, Lenski RE. 4.  2013. Genome dynamics during experimental evolution. Nat. Rev. Genet. 14:827–39 [Google Scholar]
  5. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S. 5.  et al. 2010. The landscape of somatic copy-number alteration across human cancers. Nature 463:899–905 [Google Scholar]
  6. Bignell GR, Santarius T, Pole JC, Butler AP, Perry J. 6.  et al. 2007. Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution. Genome Res. 17:1296–303 [Google Scholar]
  7. Bonassi S, El-Zein R, Bolognesi C, Fenech M. 7.  2011. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis 26:93–100 [Google Scholar]
  8. Breger KS, Smith L, Thayer MJ. 8.  2005. Engineering translocations with delayed replication: evidence for cis control of chromosome replication timing. Hum. Mol. Genet. 14:2813–27 [Google Scholar]
  9. Cai H, Kumar N, Bagheri HC, von Mering C, Robinson MD, Baudis M. 9.  2014. Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens. BMC Genomics 15:82 [Google Scholar]
  10. Campbell CD, Eichler EE. 10.  2013. Properties and rates of germline mutations in humans. Trends Genet. 29:575–84 [Google Scholar]
  11. Campbell PJ, Stephens PJ, Pleasance ED, O'Meara S, Li H. 11.  et al. 2008. Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat. Genet. 40:722–29 [Google Scholar]
  12. Carbone L, Harris RA, Gnerre S, Veeramah KR, Lorente-Galdos B. 12.  et al. 2014. Gibbon genome and the fast karyotype evolution of small apes. Nature 513:195–201 [Google Scholar]
  13. Carbone L, Harris RA, Mootnick AR, Milosavljevic A, Martin DI. 13.  et al. 2012. Centromere remodeling in Hoolock leuconedys (Hylobatidae) by a new transposable element unique to the gibbons. Genome Biol. Evol. 4:648–58 [Google Scholar]
  14. Carroll SM, DeRose ML, Gaudray P, Moore CM, Needham-Vandevanter DR. 14.  et al. 1988. Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol. Cell. Biol. 8:1525–33 [Google Scholar]
  15. Carvalho CM, Pehlivan D, Ramocki MB, Fang P, Alleva B. 15.  et al. 2013. Replicative mechanisms for CNV formation are error prone. Nat. Genet. 45:1319–26 [Google Scholar]
  16. Chan K, Gordenin DA. 16.  2015. Clusters of multiple mutations: incidence and molecular mechanisms. Annu. Rev. Genet. 49:243–67 [Google Scholar]
  17. Chen CL, Rappailles A, Duquenne L, Huvet M, Guilbaud G. 17.  et al. 2010. Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes. Genome Res. 20:447–57 [Google Scholar]
  18. Chiang C, Jacobsen JC, Ernst C, Hanscom C, Heilbut A. 18.  et al. 2012. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat. Genet. 44:390–97, S1 [Google Scholar]
  19. Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B. 19.  et al. 2011. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147:107–19 [Google Scholar]
  20. Cowell JK. 20.  1982. Double minutes and homogeneously staining regions: gene amplification in mammalian cells. Annu. Rev. Genet. 16:21–59 [Google Scholar]
  21. Cox LS. 21.  1992. DNA replication in cell-free extracts from Xenopus eggs is prevented by disrupting nuclear envelope function. J. Cell Sci. 101:Pt. 143–53 [Google Scholar]
  22. Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV. 22.  et al. 2012. DNA breaks and chromosome pulverization from errors in mitosis. Nature 482:53–58 [Google Scholar]
  23. Cremer T, Cremer M. 23.  2010. Chromosome territories. Cold Spring Harb. Perspect. Biol. 2:a003889 [Google Scholar]
  24. Curt GA, Carney DN, Cowan KH, Jolivet J, Bailey BD. 24.  et al. 1983. Unstable methotrexate resistance in human small-cell carcinoma associated with double minute chromosomes. N. Engl. J. Med. 308:199–202 [Google Scholar]
  25. Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD. 25.  et al. 2014. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell 26:319–30 [Google Scholar]
  26. Davoli T, Xu AW, Mengwasser KE, Sack LM, Yoon JC. 26.  et al. 2013. Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome. Cell 155:948–62 [Google Scholar]
  27. De Lange T. 27.  2005. Telomere-related genome instability in cancer. Cold Spring Harb. Symp. Quant. Biol. 70:197–204 [Google Scholar]
  28. de Pagter MS, van Roosmalen MJ, Baas AF, Renkens I, Duran KJ. 28.  et al. 2015. Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am. J. Hum. Genet. 96:651–56 [Google Scholar]
  29. De S, Michor F. 29.  2011. DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes. Nat. Biotechnol. 29:1103–8 [Google Scholar]
  30. Debatisse M, Le Tallec B, Letessier A, Dutrillaux B, Brison O. 30.  2012. Common fragile sites: mechanisms of instability revisited. Trends Genet. 28:22–32 [Google Scholar]
  31. Dewhurst SM, McGranahan N, Burrell RA, Rowan AJ, Gronroos E. 31.  et al. 2014. Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution. Cancer Discov. 4:175–85 [Google Scholar]
  32. Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R. 32.  et al. 2015. Sequential cancer mutations in cultured human intestinal stem cells. Nature 521:43–47 [Google Scholar]
  33. El Achkar E, Gerbault-Seureau M, Muleris M, Dutrillaux B, Debatisse M. 33.  2005. Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites. PNAS 102:18069–74 [Google Scholar]
  34. Eldredge N, Gould SJ. 34.  1972. Punctuated Equilibria: An Alternative to Phyletic Gradualism San Francisco: Freeman Cooper & Co. [Google Scholar]
  35. Fenech M. 35.  2007. Cytokinesis-block micronucleus cytome assay. Nat. Protoc. 2:1084–104 [Google Scholar]
  36. Fenech M, Kirsch-Volders M, Natarajan AT, Surralles J, Crott JW. 36.  et al. 2011. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 26:125–32 [Google Scholar]
  37. Fenech M, Morley AA. 37.  1986. Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivo ageing and low dose X-irradiation. Mutat. Res. 161:193–98 [Google Scholar]
  38. Ferguson-Smith MA, Trifonov V. 38.  2007. Mammalian karyotype evolution. Nat. Rev. Genet. 8:950–62 [Google Scholar]
  39. Fousteri M, Mullenders LH. 39.  2008. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res. 18:73–84 [Google Scholar]
  40. Francis JM, Zhang CZ, Maire CL, Jung J, Manzo VE. 40.  et al. 2014. EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 4:956–71 [Google Scholar]
  41. Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D. 41.  2005. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 437:1043–47 [Google Scholar]
  42. Ganem NJ, Godinho SA, Pellman D. 42.  2009. A mechanism linking extra centrosomes to chromosomal instability. Nature 460:278–82 [Google Scholar]
  43. Ganem NJ, Pellman D. 43.  2012. Linking abnormal mitosis to the acquisition of DNA damage. J. Cell Biol. 199:871–81 [Google Scholar]
  44. Garsed DW, Marshall OJ, Corbin VD, Hsu A, Di Stefano L. 44.  et al. 2014. The architecture and evolution of cancer neochromosomes. Cancer Cell 26:653–67 [Google Scholar]
  45. Gates WH, Papadimitriou CH. 45.  1979. Bounds for sorting by prefix reversal. Discrete Math. 27:47–57 [Google Scholar]
  46. Geraud G, Laquerriere F, Masson C, Arnoult J, Labidi B, Hernandez-Verdun D. 46.  1989. Three-dimensional organization of micronuclei induced by colchicine in PtK1 cells. Exp. Cell Res. 181:27–39 [Google Scholar]
  47. Gibaud A, Vogt N, Hadj-Hamou NS, Meyniel JP, Hupe P. 47.  et al. 2010. Extrachromosomal amplification mechanisms in a glioma with amplified sequences from multiple chromosome loci. Hum. Mol. Genet. 19:1276–85 [Google Scholar]
  48. Gisselsson D, Bjork J, Hoglund M, Mertens F, Dal Cin P. 48.  et al. 2001. Abnormal nuclear shape in solid tumors reflects mitotic instability. Am. J. Pathol. 158:199–206 [Google Scholar]
  49. Gisselsson D, Hoglund M, Mertens F, Johansson B, Dal Cin P. 49.  et al. 1999. The structure and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells. Hum. Genet. 104:315–25 [Google Scholar]
  50. Gisselsson D, Pettersson L, Hoglund M, Heidenblad M, Gorunova L. 50.  et al. 2000. Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity. PNAS 97:5357–62 [Google Scholar]
  51. Gordon DJ, Resio B, Pellman D. 51.  2012. Causes and consequences of aneuploidy in cancer. Nat. Rev. Genet. 13:189–203 [Google Scholar]
  52. Gostissa M, Alt FW, Chiarle R. 52.  2011. Mechanisms that promote and suppress chromosomal translocations in lymphocytes. Annu. Rev. Immunol. 29:319–50 [Google Scholar]
  53. Gotoh E, Asakawa Y, Kosaka H. 53.  1995. Inhibition of protein serine/threonine phosphatases directly induces premature chromosome condensation in mammalian somatic cells. Biomed. Res. 16:63–68 [Google Scholar]
  54. Greenman CD, Cooke SL, Marshall J, Stratton MR, Campbell PJ. 54.  2015. Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process. J. Math. Biol. doi:10.1007/s00285-015-0875-2 [Google Scholar]
  55. Haber JE. 55.  2014. Genome Stability: DNA Repair and Recombination New York: GS/Garland Sci./Taylor & Francis Group [Google Scholar]
  56. Hamkalo BA, Farnham PJ, Johnston R, Schimke RT. 56.  1985. Ultrastructural features of minute chromosomes in a methotrexate-resistant mouse 3T3 cell line. PNAS 82:1126–30 [Google Scholar]
  57. Hatch EM, Fischer AH, Deerinck TJ, Hetzer MW. 57.  2013. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 154:47–60 [Google Scholar]
  58. Hayashi MT, Cesare AJ, Fitzpatrick JA, Lazzerini-Denchi E, Karlseder J. 58.  2012. A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. Nat. Struct. Mol. Biol. 19:387–94 [Google Scholar]
  59. Heidenblad M, Hallor KH, Staaf J, Jonsson G, Borg A. 59.  et al. 2006. Genomic profiling of bone and soft tissue tumors with supernumerary ring chromosomes using tiling resolution bacterial artificial chromosome microarrays. Oncogene 25:7106–16 [Google Scholar]
  60. Helleday T, Eshtad S, Nik-Zainal S. 60.  2014. Mechanisms underlying mutational signatures in human cancers. Nat. Rev. Genet. 15:585–98 [Google Scholar]
  61. Hetzer MW. 61.  2010. The nuclear envelope. Cold Spring Harb. Perspect. Biol. 2:a000539 [Google Scholar]
  62. Hicks WM, Kim M, Haber JE. 62.  2010. Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329:82–85 [Google Scholar]
  63. Hodgkinson A, Chen Y, Eyre-Walker A. 63.  2012. The large-scale distribution of somatic mutations in cancer genomes. Hum. Mutat. 33:136–43 [Google Scholar]
  64. Hoffelder DR, Luo L, Burke NA, Watkins SC, Gollin SM, Saunders WS. 64.  2004. Resolution of anaphase bridges in cancer cells. Chromosoma 112:389–97 [Google Scholar]
  65. Holland AJ, Cleveland DW. 65.  2012. Chromoanagenesis and cancer: mechanisms and consequences of localized, complex chromosomal rearrangements. Nat. Med. 18:1630–38 [Google Scholar]
  66. Huang Y, Jiang L, Yi Q, Lv L, Wang Z. 66.  et al. 2012. Lagging chromosomes entrapped in micronuclei are not “lost” by cells. Cell Res. 22:932–35 [Google Scholar]
  67. Ichim G, Lopez J, Ahmed SU, Muthalagu N, Giampazolias E. 67.  et al. 2015. Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death. Mol. Cell 57:860–72 [Google Scholar]
  68. Jager N, Schlesner M, Jones DT, Raffel S, Mallm JP. 68.  et al. 2013. Hypermutation of the inactive X chromosome is a frequent event in cancer. Cell 155:567–81 [Google Scholar]
  69. Janssen A, van der Burg M, Szuhai K, Kops GJ, Medema RH. 69.  2011. Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations. Science 333:1895–98 [Google Scholar]
  70. Johnson RT, Rao PN. 70.  1970. Mammalian cell fusion: induction of premature chromosome condensation in interphase nuclei. Nature 226:717–22 [Google Scholar]
  71. Jones MJ, Jallepalli PV. 71.  2012. Chromothripsis: chromosomes in crisis. Dev. Cell 23:908–17 [Google Scholar]
  72. Joseph LJ, Bhartiya US, Raut YS, Kand P, Hawaldar RW, Nair N. 72.  2009. Micronuclei frequency in peripheral blood lymphocytes of thyroid cancer patients after radioiodine therapy and its relationship with metastasis. Mutat. Res. 675:35–40 [Google Scholar]
  73. Kato H, Sandberg AA. 73.  1967. Chromosome pulverization in human binucleate cells following colcemid treatment. J. Cell Biol. 34:35–45 [Google Scholar]
  74. Kaufman RJ, Brown PC, Schimke RT. 74.  1979. Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes. PNAS 76:5669–73 [Google Scholar]
  75. Kim TM, Xi R, Luquette LJ, Park RW, Johnson MD, Park PJ. 75.  2013. Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res. 23:217–27 [Google Scholar]
  76. Kinsella M, Bafna V. 76.  2012. Combinatorics of the breakage-fusion-bridge mechanism. J. Comput. Biol. 19:662–78 [Google Scholar]
  77. Kinsella M, Patel A, Bafna V. 77.  2014. The elusive evidence for chromothripsis. Nucleic Acids Res. 42:8231–42 [Google Scholar]
  78. Kistenmacher ML, Punnett HH. 78.  1970. Comparative behavior of ring chromosomes. Am. J. Hum. Genet. 22:304–18 [Google Scholar]
  79. Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A. 79.  et al. 2011. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147:95–106 [Google Scholar]
  80. Kloosterman WP, Cuppen E. 80.  2013. Chromothripsis in congenital disorders and cancer: similarities and differences. Curr. Opin. Cell Biol. 25:341–48 [Google Scholar]
  81. Kloosterman WP, Guryev V, van Roosmalen M, Duran KJ, de Bruijn E. 81.  et al. 2011. Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Hum. Mol. Genet. 20:1916–24 [Google Scholar]
  82. Kloosterman WP, Koster J, Molenaar JJ. 82.  2014. Prevalence and clinical implications of chromothripsis in cancer genomes. Curr. Opin. Oncol. 26:64–72 [Google Scholar]
  83. Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I. 83.  et al. 2012. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. Cell Rep. 1:648–55 [Google Scholar]
  84. Knudson AG Jr. 84.  1971. Mutation and cancer: statistical study of retinoblastoma. PNAS 68:820–23 [Google Scholar]
  85. Korbel JO, Campbell PJ. 85.  2013. Criteria for inference of chromothripsis in cancer genomes. Cell 152:1226–36 [Google Scholar]
  86. Koren A, Polak P, Nemesh J, Michaelson JJ, Sebat J. 86.  et al. 2012. Differential relationship of DNA replication timing to different forms of human mutation and variation. Am. J. Hum. Genet. 91:1033–40 [Google Scholar]
  87. Lane DP. 87.  1992. Cancer. p53, guardian of the genome. Nature 358:15–16 [Google Scholar]
  88. Lang GI, Murray AW. 88.  2008. Estimating the per-base-pair mutation rate in the yeast Saccharomyces cerevisiae. Genetics 178:67–82 [Google Scholar]
  89. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K. 89.  et al. 2013. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499:214–18 [Google Scholar]
  90. Le Tallec B, Millot GA, Blin ME, Brison O, Dutrillaux B, Debatisse M. 90.  2013. Common fragile site profiling in epithelial and erythroid cells reveals that most recurrent cancer deletions lie in fragile sites hosting large genes. Cell Rep. 4:420–28 [Google Scholar]
  91. Leach NT, Jackson-Cook C. 91.  2004. Micronuclei with multiple copies of the X chromosome: Do chromosomes replicate in micronuclei?. Mutat. Res. 554:89–94 [Google Scholar]
  92. Lee JA, Carvalho CM, Lupski JR. 92.  2007. A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders. Cell 131:1235–47 [Google Scholar]
  93. Lemaitre JM, Geraud G, Mechali M. 93.  1998. Dynamics of the genome during early Xenopus laevis development: karyomeres as independent units of replication. J. Cell Biol. 142:1159–66 [Google Scholar]
  94. Levine AJ. 94.  1997. p53, the cellular gatekeeper for growth and division. Cell 88:323–31 [Google Scholar]
  95. Li Y, Schwab C, Ryan SL, Papaemmanuil E, Robinson HM. 95.  et al. 2014. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 508:98–102 [Google Scholar]
  96. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T. 96.  et al. 2009. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–93 [Google Scholar]
  97. Liu L, De S, Michor F. 97.  2013. DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes. Nat. Commun. 4:1502 [Google Scholar]
  98. Liu P, Carvalho CM, Hastings PJ, Lupski JR. 98.  2012. Mechanisms for recurrent and complex human genomic rearrangements. Curr. Opin. Genet. Dev. 22:211–20 [Google Scholar]
  99. Liu P, Erez A, Nagamani SC, Dhar SU, Kolodziejska KE. 99.  et al. 2011. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell 146:889–903 [Google Scholar]
  100. Louis-Brennetot C, Coindre JM, Ferreira C, Perot G, Terrier P, Aurias A. 100.  2011. The CDKN2A/CDKN2B/CDK4/CCND1 pathway is pivotal in well-differentiated and dedifferentiated liposarcoma oncogenesis: an analysis of 104 tumors.. Genes Chromosomes Cancer 50:896–907 [Google Scholar]
  101. Lukas C, Savic V, Bekker-Jensen S, Doil C, Neumann B. 101.  et al. 2011. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress. Nat. Cell Biol. 13:243–53 [Google Scholar]
  102. Lynch M. 102.  2010. Rate, molecular spectrum, and consequences of human mutation. PNAS 107:961–68 [Google Scholar]
  103. Malhotra A, Lindberg M, Faust GG, Leibowitz ML, Clark RA. 103.  et al. 2013. Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms. Genome Res. 23:762–76 [Google Scholar]
  104. Mardin BR, Drainas AP, Waszak SM, Weischenfeldt J, Isokane M. 103a.  et al. 2015. A cell-based model system links chromothripsis with hyperploidy. Mol. Syst. Biol. 11:828 [Google Scholar]
  105. McClintock B. 104.  1938. The production of homozygous deficient tissues with mutant characteristics by means of the aberrant mitotic behavior of ring-shaped chromosomes. Genetics 23:315–76 [Google Scholar]
  106. McClintock B. 105.  1941. The stability of broken ends of chromosomes in Zea mays. Genetics 26:234–82 [Google Scholar]
  107. McDermott DH, Gao JL, Liu Q, Siwicki M, Martens C. 106.  et al. 2015. Chromothriptic cure of WHIM syndrome. Cell 160:686–99 [Google Scholar]
  108. Meaburn KJ, Misteli T, Soutoglou E. 107.  2007. Spatial genome organization in the formation of chromosomal translocations. Semin. Cancer Biol. 17:80–90 [Google Scholar]
  109. Mills RE, Walter K, Stewart C, Handsaker RE, Chen K. 108.  et al. 2011. Mapping copy number variation by population-scale genome sequencing. Nature 470:59–65 [Google Scholar]
  110. Misteli T, Soutoglou E. 109.  2009. The emerging role of nuclear architecture in DNA repair and genome maintenance. Nat. Rev. Mol. Cell Biol. 10:243–54 [Google Scholar]
  111. Murgia E, Ballardin M, Bonassi S, Rossi AM, Barale R. 110.  2008. Validation of micronuclei frequency in peripheral blood lymphocytes as early cancer risk biomarker in a nested case-control study. Mutat. Res. 639:27–34 [Google Scholar]
  112. Murray JE, van der Burg M, IJspeert H, Carroll P, Wu Q. 111.  et al. 2015. Mutations in the NHEJ component XRCC4 cause primordial dwarfism. Am. J. Hum. Genet. 96:412–24 [Google Scholar]
  113. Naim V, Rosselli F. 112.  2009. The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities. Nat. Cell Biol. 11:761–68 [Google Scholar]
  114. Naim V, Wilhelm T, Debatisse M, Rosselli F. 113.  2013. ERCC1 and MUS81-EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis. Nat. Cell Biol. 15:1008–15 [Google Scholar]
  115. Nathanson DA, Gini B, Mottahedeh J, Visnyei K, Koga T. 114.  et al. 2014. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343:72–76 [Google Scholar]
  116. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD. 115.  et al. 2012. Mutational processes molding the genomes of 21 breast cancers. Cell 149:979–93 [Google Scholar]
  117. Obe G, Beek B. 116.  1982. Premature chromosome condensation in micronuclei. See Ref. 123 113–30
  118. Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J. 117.  et al. 2015. Whole-genome characterization of chemoresistant ovarian cancer. Nature 521:489–94 [Google Scholar]
  119. Pedersen RT, Kruse T, Nilsson J, Oestergaard VH, Lisby M. 118.  2015. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells. J. Cell Biol. 210:565–82 [Google Scholar]
  120. Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G. 119.  et al. 1999. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 24:30–41 [Google Scholar]
  121. Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ. 120.  et al. 2010. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463:191–96 [Google Scholar]
  122. Rajagopalan H, Jallepalli PV, Rago C, Velculescu VE, Kinzler KW. 121.  et al. 2004. Inactivation of hCDC4 can cause chromosomal instability. Nature 428:77–81 [Google Scholar]
  123. Ranz JM, Casals F, Ruiz A. 122.  2001. How malleable is the eukaryotic genome? Extreme rate of chromosomal rearrangement in the genus Drosophila. Genome Res. 11:230–39 [Google Scholar]
  124. Rao PN, Johnson RT, Sperling K. 123.  1982. Premature Chromosome Condensation: Application in Basic, Clinical, and Mutation Research New York: Academic [Google Scholar]
  125. Rao X, Zhang Y, Yi Q, Hou H, Xu B. 124.  et al. 2008. Multiple origins of spontaneously arising micronuclei in HeLa cells: direct evidence from long-term live cell imaging. Mutat. Res. 646:41–49 [Google Scholar]
  126. Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T. 125.  et al. 2012. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148:59–71 [Google Scholar]
  127. Ravi M, Marimuthu MP, Tan EH, Maheshwari S, Henry IM. 126.  et al. 2014. A haploid genetics toolbox for Arabidopsis thaliana. Nat. Commun. 5:5334 [Google Scholar]
  128. Robberecht C, Voet T, Zamani Esteki M, Nowakowska BA, Vermeesch JR. 127.  2013. Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations. Genome Res. 23:411–18 [Google Scholar]
  129. Roberts SA, Sterling J, Thompson C, Harris S, Mav D. 128.  et al. 2012. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol. Cell 46:424–35 [Google Scholar]
  130. Rubin AF, Green P. 129.  2009. Mutation patterns in cancer genomes. PNAS 106:21766–70 [Google Scholar]
  131. Sanborn JZ, Salama SR, Grifford M, Brennan CW, Mikkelsen T. 130.  et al. 2013. Double minute chromosomes in glioblastoma multiforme are revealed by precise reconstruction of oncogenic amplicons. Cancer Res. 73:6036–45 [Google Scholar]
  132. Sazer S, Lynch M, Needleman D. 131.  2014. Deciphering the evolutionary history of open and closed mitosis. Curr. Biol. 24:R1099–103 [Google Scholar]
  133. Schuster-Bockler B, Lehner B. 132.  2012. Chromatin organization is a major influence on regional mutation rates in human cancer cells. Nature 488:504–7 [Google Scholar]
  134. Sen S, Hittelman WN, Teeter LD, Kuo MT. 133.  1989. Model for the formation of double minutes from prematurely condensed chromosomes of replicating micronuclei in drug-treated Chinese hamster ovary cells undergoing DNA amplification. Cancer Res. 49:6731–37 [Google Scholar]
  135. Sharp AJ, Locke DP, McGrath SD, Cheng Z, Bailey JA. 134.  et al. 2005. Segmental duplications and copy-number variation in the human genome. Am. J. Hum. Genet. 77:78–88 [Google Scholar]
  136. Sheltzer JM, Blank HM, Pfau SJ, Tange Y, George BM. 135.  et al. 2011. Aneuploidy drives genomic instability in yeast. Science 333:1026–30 [Google Scholar]
  137. Shima N, Hartford SA, Duffy T, Wilson LA, Schimenti KJ, Schimenti JC. 136.  2003. Phenotype-based identification of mouse chromosome instability mutants. Genetics 163:1031–40 [Google Scholar]
  138. Snuderl M, Fazlollahi L, Le LP, Nitta M, Zhelyazkova BH. 137.  et al. 2011. Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell 20:810–17 [Google Scholar]
  139. Stamatoyannopoulos JA, Adzhubei I, Thurman RE, Kryukov GV, Mirkin SM, Sunyaev SR. 138.  2009. Human mutation rate associated with DNA replication timing. Nat. Genet. 41:393–95 [Google Scholar]
  140. Stankiewicz P, Lupski JR. 139.  2002. Molecular-evolutionary mechanisms for genomic disorders. Curr. Opin. Genet. Dev. 12:312–19 [Google Scholar]
  141. Stark GR, Wahl GM. 140.  1984. Gene amplification. Annu. Rev. Biochem. 53:447–91 [Google Scholar]
  142. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR. 141.  et al. 2011. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144:27–40 [Google Scholar]
  143. Stephens PJ, McBride DJ, Lin ML, Varela I, Pleasance ED. 142.  et al. 2009. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 462:1005–10 [Google Scholar]
  144. Storchova Z, Breneman A, Cande J, Dunn J, Burbank K. 143.  et al. 2006. Genome-wide genetic analysis of polyploidy in yeast. Nature 443:541–47 [Google Scholar]
  145. Storlazzi CT, Lonoce A, Guastadisegni MC, Trombetta D, D'Addabbo P. 144.  et al. 2010. Gene amplification as double minutes or homogeneously staining regions in solid tumors: origin and structure. Genome Res. 20:1198–206 [Google Scholar]
  146. Supek F, Lehner B. 145.  2015. Differential DNA mismatch repair underlies mutation rate variation across the human genome. Nature 521:81–84 [Google Scholar]
  147. Symington LS, Gautier J. 146.  2011. Double-strand break end resection and repair pathway choice. Annu. Rev. Genet. 45:247–71 [Google Scholar]
  148. Szerlip NJ, Pedraza A, Chakravarty D, Azim M, McGuire J. 147.  et al. 2012. Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. PNAS 109:3041–46 [Google Scholar]
  149. Tan EH, Henry IM, Ravi M, Bradnam KR, Mandakova T. 148.  et al. 2015. Catastrophic chromosomal restructuring during genome elimination in plants. eLife 4:e06516 [Google Scholar]
  150. Taylor BJ, Nik-Zainal S, Wu YL, Stebbings LA, Raine K. 149.  et al. 2013. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. eLife 2:e00534 [Google Scholar]
  151. Taylor BS, DeCarolis PL, Angeles CV, Brenet F, Schultz N. 150.  et al. 2011. Frequent alterations and epigenetic silencing of differentiation pathway genes in structurally rearranged liposarcomas. Cancer Discov. 1:587–97 [Google Scholar]
  152. Teles Alves I, Hiltemann S, Hartjes T, van der Spek P, Stubbs A. 151.  et al. 2013. Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line. Hum. Genet. 132:709–13 [Google Scholar]
  153. Terradas M, Martín M, Hernández L, Tusell L, Genescá A. 152.  2012. Nuclear envelope defects impede a proper response to micronuclear DNA lesions. Mutat. Res. 729:35–40 [Google Scholar]
  154. Terradas M, Martin M, Tusell L, Genescá A. 153.  2009. DNA lesions sequestered in micronuclei induce a local defective-damage response. DNA Repair 8:1225–34 [Google Scholar]
  155. Terradas M, Martín M, Tusell L, Genescá A. 154.  2010. Genetic activities in micronuclei: Is the DNA entrapped in micronuclei lost for the cell?. Mutat. Res. 705:60–67 [Google Scholar]
  156. Thompson SL, Compton DA. 155.  2011. Chromosome missegregation in human cells arises through specific types of kinetochore-microtubule attachment errors. PNAS 108:17974–78 [Google Scholar]
  157. Toledo LI, Altmeyer M, Rask MB, Lukas C, Larsen DH. 156.  et al. 2013. ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 155:1088–103 [Google Scholar]
  158. Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M. 157.  et al. 2007. Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317:916–24 [Google Scholar]
  159. Tubio JM, Estivill X. 158.  2011. Cancer: when catastrophe strikes a cell. Nature 470:476–77 [Google Scholar]
  160. Vogelstein B, Lane D, Levine AJ. 159.  2000. Surfing the p53 network. Nature 408:307–10 [Google Scholar]
  161. Vogt N, Lefevre SH, Apiou F, Dutrillaux AM, Cor A. 160.  et al. 2004. Molecular structure of double-minute chromosomes bearing amplified copies of the epidermal growth factor receptor gene in gliomas. PNAS 101:11368–73 [Google Scholar]
  162. Von Hoff DD, McGill JR, Forseth BJ, Davidson KK, Bradley TP. 161.  et al. 1992. Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity. PNAS 89:8165–69 [Google Scholar]
  163. Von Hoff DD, Needham-VanDevanter DR, Yucel J, Windle BE, Wahl GM. 162.  1988. Amplified human MYC oncogenes localized to replicating submicroscopic circular DNA molecules. PNAS 85:4804–8 [Google Scholar]
  164. Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS. 163.  et al. 2015. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518:495–501 [Google Scholar]
  165. Wahl GM. 164.  1989. The importance of circular DNA in mammalian gene amplification. Cancer Res. 49:1333–40 [Google Scholar]
  166. Wang X, Asmann YW, Erickson-Johnson MR, Oliveira JL, Zhang H. 165.  et al. 2011. High-resolution genomic mapping reveals consistent amplification of the fibroblast growth factor receptor substrate 2 gene in well-differentiated and dedifferentiated liposarcoma. Genes Chromosomes Cancer 50:849–58 [Google Scholar]
  167. Windle B, Draper BW, Yin YX, O'Gorman S, Wahl GM. 166.  1991. A central role for chromosome breakage in gene amplification, deletion formation, and amplicon integration. Genes Dev. 5:160–74 [Google Scholar]
  168. Woo YH, Li WH. 167.  2012. DNA replication timing and selection shape the landscape of nucleotide variation in cancer genomes. Nat. Commun. 3:1004 [Google Scholar]
  169. Xing J, Zhang Y, Han K, Salem AH, Sen SK. 168.  et al. 2009. Mobile elements create structural variation: analysis of a complete human genome. Genome Res. 19:1516–26 [Google Scholar]
  170. Yang L, Luquette LJ, Gehlenborg N, Xi R, Haseley PS. 169.  et al. 2013. Diverse mechanisms of somatic structural variations in human cancer genomes. Cell 153:919–29 [Google Scholar]
  171. Yates LR, Campbell PJ. 170.  2012. Evolution of the cancer genome. Nat. Rev. Genet. 13:795–806 [Google Scholar]
  172. Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G. 171.  et al. 2013. Pan-cancer patterns of somatic copy number alteration. Nat. Genet. 45:1134–40 [Google Scholar]
  173. Zhang F, Carvalho CM, Lupski JR. 172.  2009. Complex human chromosomal and genomic rearrangements. Trends Genet. 25:298–307 [Google Scholar]
  174. Zhang CZ, Leibowitz ML, Pellman D. 173.  2013. Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements. Genes Dev. 27:2513–30 [Google Scholar]
  175. Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK. 174.  et al. 2015. Chromothripsis from DNA damage in micronuclei. Nature 522:179–84 [Google Scholar]
  176. Zhao R, Deibler RW, Lerou PH, Ballabeni A, Heffner GC. 175.  et al. 2014. A nontranscriptional role for Oct4 in the regulation of mitotic entry. PNAS 111:15768–73 [Google Scholar]
  177. zur Hausen H. 176.  1967. Chromosomal changes of similar nature in seven established cell lines derived from the peripheral blood of patients with leukemia. J. Natl. Cancer Inst. 38:683–96 [Google Scholar]
/content/journals/10.1146/annurev-genet-120213-092228
Loading
/content/journals/10.1146/annurev-genet-120213-092228
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error