REFERENCES
1. Martelotto LG, Ng CK, Piscuoglio S, Weigelt B, Reis-Filho JS. Breast cancer intra-tumor heterogeneity. Breast Cancer Res 2014;16:210.
2. Andor N, Graham TA, Jansen M, Xia LC, Aktipis CA, Petritsch C, Ji HP, Maley CC. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. Nat Med 2016;22:105-13.
3. Caswell DR, Swanton C. The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome. BMC Med 2017;15:133.
4. McClelland SE, Burrell RA, Swanton C. Chromosomal instability: a composite phenotype that influences sensitivity to chemotherapy. Cell Cycle 2009;8:3262-6.
5. Burrell RA, McGranahan N, Bartek J, Swanton C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature 2013;501:338-45.
6. Morrissy AS, Cavalli FMG, Remke M, Ramaswamy V, Shih DJH, Holgado BL, Farooq H, Donovan LK, Garzia L, Agnihotri S, Kiehna EN, Mercier E, Mayoh C, Papillon-Cavanagh S, Nikbakht H, Gayden T, Torchia J, Picard D, Merino DM, Vladoiu M, Luu B, Wu X, Daniels C, Horswell S, Thompson YY, Hovestadt V, Northcott PA, Jones DTW, Peacock J, Wang X, Mack SC, Reimand J, Albrecht S, Fontebasso AM, Thiessen N, Li Y, Schein JE, Lee D, Carlsen R, Mayo M, Tse K, Tam A, Dhalla N, Ally A, Chuah E, Cheng Y, Plettner P, Li HI, Corbett RD, Wong T, Long W, Loukides J, Buczkowicz P, Hawkins CE, Tabori U, Rood BR, Myseros JS, Packer RJ, Korshunov A, Lichter P, Kool M, Pfister SM, Schuller U, Dirks P, Huang A, Bouffet E, Rutka JT, Bader GD, Swanton C, Ma Y, Moore RA, Mungall AJ, Majewski J, Jones SJM, Das S, Malkin D, Jabado N, Marra MA, Taylor MD. Spatial heterogeneity in medulloblastoma. Nat Genet 2017;49:780-8.
7. Ulintz PJ, Greenson JK, Wu R, Fearon ER, Hardiman KM. Lymph node metastases in colon cancer are polyclonal. Clin Cancer Res 2018;24:2214-24.
8. McPherson A, Roth A, Laks E, Masud T, Bashashati A, Zhang AW, Ha G, Biele J, Yap D, Wan A, Prentice LM, Khattra J, Smith MA, Nielsen CB, Mullaly SC, Kalloger S, Karnezis A, Shumansky K, Siu C, Rosner J, Chan HL, Ho J, Melnyk N, Senz J, Yang W, Moore R, Mungall AJ, Marra MA, Bouchard-Cote A, Gilks CB, Huntsman DG, McAlpine JN, Aparicio S, Shah SP. Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer. Nat Genet 2016;48:758-67.
9. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature 2000;406:747-52.
10. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003;100:8418-23.
11. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869-74.
12. Roylance R, Endesfelder D, Gorman P, Burrell RA, Sander J, Tomlinson I, Hanby AM, Speirs V, Richardson AL, Birkbak NJ, Eklund AC, Downward J, Kschischo M, Szallasi Z, Swanton C. Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol Biomarkers Prev 2011;20:2183-94.
13. Denu RA, Zasadil LM, Kanugh C, Laffin J, Weaver BA, Burkard ME. Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer. BMC Cancer 2016;16:47.
14. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 2007;13:2329-34.
15. Jin L, Han B, Siegel E, Cui Y, Giuliano A, Cui X. Breast cancer lung metastasis: Molecular biology and therapeutic implications. Cancer Biol Ther 2018; doi: 10.1080/15384047.2018.1456599:1-11.
16. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, Perreard L, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, Perou CM. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006;7:96.
17. Sansregret L, Swanton C. The role of aneuploidy in cancer evolution. Cold Spring Harb Perspect Med 2017;7:a028373.
18. Lee AJ, Endesfelder D, Rowan AJ, Walther A, Birkbak NJ, Futreal PA, Downward J, Szallasi Z, Tomlinson IP, Howell M, Kschischo M, Swanton C. Chromosomal instability confers intrinsic multidrug resistance. Cancer Res 2011;71:1858-70.
21. Loeb LA. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 1991;51:3075-9.
22. Fukasawa K, Wiener F, Vande Woude GF, Mai S. Genomic instability and apoptosis are frequent in p53 deficient young mice. Oncogene 1997;15:1295-302.
23. Tutt A, Gabriel A, Bertwistle D, Connor F, Paterson H, Peacock J, Ross G, Ashworth A. Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification. Curr Biol 1999;9:1107-10.
24. Xu X, Weaver Z, Linke SP, Li C, Gotay J, Wang XW, Harris CC, Ried T, Deng CX. Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. Mol Cell 1999;3:389-95.
25. Zeng X, Shaikh FY, Harrison MK, Adon AM, Trimboli AJ, Carroll KA, Sharma N, Timmers C, Chodosh LA, Leone G, Saavedra HI. The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2. Oncogene 2010;29:5103-12.
26. Saavedra HI, Knauf JA, Shirokawa JM, Wang J, Ouyang B, Elisei R, Stambrook PJ, Fagin JA. The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway. Oncogene 2000;19:3948-54.
27. Saavedra HI, Fukasawa K, Conn CW, Stambrook PJ. MAPK mediates RAS-induced chromosome instability. J Biol Chem 1999;274:38083-90.
28. Felsher DW, Bishop JM. Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc Natl Acad Sci U S A 1999;96:3940-4.
29. Weaver ZA, McCormack SJ, Liyanage M, du Manoir S, Coleman A, Schrock E, Dickson RB, Ried T. A recurring pattern of chromosomal aberrations in mammary gland tumors of MMTV-cmyc transgenic mice. Genes Chromosomes Cancer 1999;25:251-60.
30. Meyerson M, Pellman D. Cancer genomes evolve by pulverizing single chromosomes. Cell 2011;144:9-10.
31. Zhang CZ, Leibowitz ML, Pellman D. Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements. Genes Dev 2013;27:2513-30.
32. Wang Y, Jin F, Higgins R, McKnight K. The current view for the silencing of the spindle assembly checkpoint. Cell Cycle 2014;13:1694-701.
34. Suijkerbuijk SJ, Kops GJ. Preventing aneuploidy: the contribution of mitotic checkpoint proteins. Biochim Biophys Acta 2008;1786:24-31.
35. Lee M, Rivera-Rivera Y, Moreno CS, Saavedra HI. The E2F activators control multiple mitotic regulators and maintain genomic integrity through Sgo1 and BubR1. Oncotarget 2017;8:77649-72.
36. Cappelletti V, Iorio E, Miodini P, Silvestri M, Dugo M, Daidone MG. Metabolic footprints and molecular subtypes in breast cancer. Dis Markers 2017;2017:7687851.
37. Grande S, Palma A, Ricci-Vitiani L, Luciani AM, Buccarelli M, Biffoni M, Molinari A, Calcabrini A, D'Amore E, Guidoni L, Pallini R, Viti V, Rosi A. Metabolic heterogeneity evidenced by MRS among patient-derived glioblastoma multiforme stem-like cells accounts for cell clustering and different responses to drugs. Stem Cells Int 2018;2018:3292704.
38. Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 2004;14:43-7.
39. Ellsworth DL, Blackburn HL, Shriver CD, Rabizadeh S, Soon-Shiong P, Ellsworth RE. Single-cell sequencing and tumorigenesis: improved understanding of tumor evolution and metastasis. Clin Transl Med 2017;6:15.
40. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012;21:283-96.
41. Navin NE. The first five years of single-cell cancer genomics and beyond. Genome Res 2015;25:1499-507.
42. Alizadeh AA, Aranda V, Bardelli A, Blanpain C, Bock C, Borowski C, Caldas C, Califano A, Doherty M, Elsner M, Esteller M, Fitzgerald R, Korbel JO, Lichter P, Mason CE, Navin N, Pe'er D, Polyak K, Roberts CW, Siu L, Snyder A, Stower H, Swanton C, Verhaak RG, Zenklusen JC, Zuber J, Zucman-Rossi J. Toward understanding and exploiting tumor heterogeneity. Nat Med 2015;21:846-53.
43. Ding L, Raphael BJ, Chen F, Wendl MC. Advances for studying clonal evolution in cancer. Cancer Lett 2013;340:212-9.
44. Trikha P, Sharma N, Pena C, Reyes A, Pecot T, Khurshid S, Rawahneh M, Moffitt J, Stephens JA, Fernandez SA, Ostrowski MC, Leone G. E2f3 in tumor macrophages promotes lung metastasis. Oncogene 2016;35:3636-46.
45. Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M. Tumour evolution inferred by single-cell sequencing. Nature 2011;472:90-4.
46. Wills QF, Mead AJ. Application of single-cell genomics in cancer: promise and challenges. Hum Mol Genet 2015;24:R74-84.
47. Zhu S, Qing T, Zheng Y, Jin L, Shi L. Advances in single-cell RNA sequencing and its applications in cancer research. Oncotarget 2017;8:53763-79.
48. Ting DT, Wittner BS, Ligorio M, Vincent Jordan N, Shah AM, Miyamoto DT, Aceto N, Bersani F, Brannigan BW, Xega K, Ciciliano JC, Zhu H, MacKenzie OC, Trautwein J, Arora KS, Shahid M, Ellis HL, Qu N, Bardeesy N, Rivera MN, Deshpande V, Ferrone CR, Kapur R, Ramaswamy S, Shioda T, Toner M, Maheswaran S, Haber DA. Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep 2014;8:1905-18.
49. Navin N, Hicks J. Future medical applications of single-cell sequencing in cancer. Genome Med 2011;3:31.
50. Ren SC, Qu M, Sun YH. Investigating intratumour heterogeneity by single-cell sequencing. Asian J Androl 2013;15:729-34.
51. Gawad C, Koh W, Quake SR. Single-cell genome sequencing: current state of the science. Nat Rev Genet 2016;17:175-88.
52. Dean FB, Hosono S, Fang L, Wu X, Faruqi AF, Bray-Ward P, Sun Z, Zong Q, Du Y, Du J, Driscoll M, Song W, Kingsmore SF, Egholm M, Lasken RS. Comprehensive human genome amplification using multiple displacement amplification. Proc Natl Acad Sci U S A 2002;99:5261-6.
53. Zong C, Lu S, Chapman AR, Xie XS. Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 2012;338:1622-6.
54. Dean FB, Nelson JR, Giesler TL, Lasken RS. Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification. Genome Res 2001;11:1095-9.
55. Spits C, Le Caignec C, De Rycke M, Van Haute L, Van Steirteghem A, Liebaers I, Sermon K. Whole-genome multiple displacement amplification from single cells. Nat Protoc 2006;1:1965-70.
56. Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, Wang X, Bodeau J, Tuch BB, Siddiqui A, Lao K, Surani MA. mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 2009;6:377-82.
57. Picelli S, Bjorklund AK, Faridani OR, Sagasser S, Winberg G, Sandberg R. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat Methods 2013;10:1096-8.
58. Ramskold D, Luo S, Wang YC, Li R, Deng Q, Faridani OR, Daniels GA, Khrebtukova I, Loring JF, Laurent LC, Schroth GP, Sandberg R. Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nat Biotechnol 2012;30:777-82.
59. Sasagawa Y, Nikaido I, Hayashi T, Danno H, Uno KD, Imai T, Ueda HR. Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity. Genome Biol 2013;14:R31.
60. Hashimshony T, Wagner F, Sher N, Yanai I. CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep 2012;2:666-73.
61. Hashimshony T, Senderovich N, Avital G, Klochendler A, de Leeuw Y, Anavy L, Gennert D, Li S, Livak KJ, Rozenblatt-Rosen O, Dor Y, Regev A, Yanai I. CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq. Genome Biol 2016;17:77.
62. Islam S, Kjallquist U, Moliner A, Zajac P, Fan JB, Lonnerberg P, Linnarsson S. Highly multiplexed and strand-specific single-cell RNA 5' end sequencing. Nat Protoc 2012;7:813-28.
63. Esparza-Lopez J, Escobar-Arriaga E, Soto-Germes S, Ibarra-Sanchez MJ. Breast cancer intra-tumor heterogeneity: one tumor, different entities. Rev Invest Clin 2017;69:66-76.
64. Pan X, Durrett RE, Zhu H, Tanaka Y, Li Y, Zi X, Marjani SL, Euskirchen G, Ma C, Lamotte RH, Park IH, Snyder MP, Mason CE, Weissman SM. Two methods for full-length RNA sequencing for low quantities of cells and single cells. Proc Natl Acad Sci U S A 2013;110:594-9.
65. Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Ferrante TC, Terry R, Turczyk BM, Yang JL, Lee HS, Aach J, Zhang K, Church GM. Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact cells and tissues. Nat Protoc 2015;10:442-58.
66. Islam S, Zeisel A, Joost S, La Manno G, Zajac P, Kasper M, Lonnerberg P, Linnarsson S. Quantitative single-cell RNA-seq with unique molecular identifiers. Nat Methods 2014;11:163-6.
67. Pollen AA, Nowakowski TJ, Shuga J, Wang X, Leyrat AA, Lui JH, Li N, Szpankowski L, Fowler B, Chen P, Ramalingam N, Sun G, Thu M, Norris M, Lebofsky R, Toppani D, Kemp DW 2nd, Wong M, Clerkson B, Jones BN, Wu S, Knutsson L, Alvarado B, Wang J, Weaver LS, May AP, Jones RC, Unger MA, Kriegstein AR, West JA. Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nat Biotechnol 2014;32:1053-8.
68. Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 2015;161:1187-201.
69. Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, Trombetta JJ, Weitz DA, Sanes JR, Shalek AK, Regev A, McCarroll SA. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 2015;161:1202-14.
70. Fan HC, Fu GK, Fodor SP. Expression profiling. Combinatorial labeling of single cells for gene expression cytometry. Science 2015;347:1258367.
71. Fan X, Zhang X, Wu X, Guo H, Hu Y, Tang F, Huang Y. Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol 2015;16:148.
72. Macaulay IC, Haerty W, Kumar P, Li YI, Hu TX, Teng MJ, Goolam M, Saurat N, Coupland P, Shirley LM, Smith M, Van der Aa N, Banerjee R, Ellis PD, Quail MA, Swerdlow HP, Zernicka-Goetz M, Livesey FJ, Ponting CP, Voet T. G&T-seq: parallel sequencing of single-cell genomes and transcriptomes. Nat Methods 2015;12:519-22.
73. Thomsen ER, Mich JK, Yao Z, Hodge RD, Doyle AM, Jang S, Shehata SI, Nelson AM, Shapovalova NV, Levi BP, Ramanathan S. Fixed single-cell transcriptomic characterization of human radial glial diversity. Nat Methods 2016;13:87-93.
74. Hu Y, Huang K, An Q, Du G, Hu G, Xue J, Zhu X, Wang CY, Xue Z, Fan G. Simultaneous profiling of transcriptome and DNA methylome from a single cell. Genome Biol 2016;17:88.
75. Hou Y, Guo H, Cao C, Li X, Hu B, Zhu P, Wu X, Wen L, Tang F, Huang Y, Peng J. Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res 2016;26:304-19.
76. Habib N, Li Y, Heidenreich M, Swiech L, Avraham-Davidi I, Trombetta JJ, Hession C, Zhang F, Regev A. Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons. Science 2016;353:925-8.
77. Nichterwitz S, Chen G, Aguila Benitez J, Yilmaz M, Storvall H, Cao M, Sandberg R, Deng Q, Hedlund E. Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling. Nat Commun 2016;7:12139.
78. Faridani OR, Abdullayev I, Hagemann-Jensen M, Schell JP, Lanner F, Sandberg R. Single-cell sequencing of the small-RNA transcriptome. Nat Biotechnol 2016;34:1264-6.
79. Turner NC, Reis-Filho JS. Genetic heterogeneity and cancer drug resistance. Lancet Oncol 2012;13:e178-85.
80. Boveri T. Concerning the Origins of Malignant Tumors. England: The Company of Biologists Limited and Cold Spring Harbor Laboratory Press; 2007.
81. Bettencourt-Dias M, Glover DM. Centrosome biogenesis and function: centrosomics brings new understanding. Nat Rev Mol Cell Biol 2007;8:451-63.
83. Paintrand M, Moudjou M, Delacroix H, Bornens M. Centrosome organization and centriole architecture: their sensitivity to divalent cations. J Struct Biol 1992;108:107-28.
85. Doxsey S. Duplicating dangerously: linking centrosome duplication and aneuploidy. Mol Cell 2002;10:439-40.
86. Hinchcliffe EH, Sluder G. "It takes two to tango": understanding how centrosome duplication is regulated throughout the cell cycle. Genes Dev 2001;15:1167-81.
87. Harrison MK, Adon AM, Saavedra HI. The G1 phase Cdks regulate the centrosome cycle and mediate oncogene-dependent centrosome amplification. Cell Div 2010;6:2.
89. Uetake Y, Loncarek J, Nordberg JJ, English CN, La Terra S, Khodjakov A, Sluder G. Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells. J Cell Biol 2007;176:173-82.
90. Hinchcliffe EH, Miller FJ, Cham M, Khodjakov A, Sluder G. Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 2001;291:1547-50.
91. Mikule K, Delaval B, Kaldis P, Jurcyzk A, Hergert P, Doxsey S. Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest. Nat Cell Biol 2007;9:160-70.
92. Pihan GA, Purohit A, Wallace J, Knecht H, Woda B, Quesenberry P, Doxsey SJ. Centrosome defects and genetic instability in malignant tumors. Cancer Res 1998;58:3974-85.
93. Lingle WL, Lutz WH, Ingle JN, Maihle NJ, Salisbury JL. Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proc Natl Acad Sci U S A 1998;95:2950-5.
94. Chan JY. A clinical overview of centrosome amplification in human cancers. Int J Biol Sci 2011;7:1122-44.
95. Sluder G, Lewis K. Relationship between nuclear DNA synthesis and centrosome reproduction in sea urchin eggs. J Exp Zool 1987;244:89-100.
97. Hinchcliffe EH, Li C, Thompson EA, Maller JL, Sluder G. Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts. [see comments.]. Science 1999;283:851-4.
98. Hinchcliffe EH, Sluder G. "It takes two to tango": understanding how centrosome duplication is regulated throughout the cell cycle. Genes Dev 2001;15:1167-81.
99. Harrison MK, Adon AM, Saavedra HI. The G1 phase Cdks regulate the centrosome cycle and mediate oncogene-dependent centrosome amplification. Cell Div 2011;6:2.
101. Godinho SA, Pellman D. Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Sci 2014;369:20130467.
102. Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE, Fukasawa K. Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell 2000;103:127-40.
103. Tokuyama Y, Horn HF, Kawamura K, Tarapore P, Fukasawa K. Specific phosphorylation of nucleophosmin on Thr(199) by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication. J Biol Chem 2001;276:21529-37.
104. Adon AM, Zeng X, Harrison MK, Sannem S, Kiyokawa H, Kaldis P, Saavedra HI. Cdk2 and Cdk4 regulate the centrosome cycle and are critical mediators of centrosome amplification in p53-null cells. Mol Cell Biol 2010;30:694-710.
105. Tokuyama Y, Horn HF, Kawamura K, Tarapore P, Fukasawa K. Specific phosphorylation of nucleophosmin on Thr(199) by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication. J Biol Chem 2001;276:21529-37.
106. Matsumoto Y, Hayashi K, Nishida E. Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells. Curr Biol 1999;9:429-32.
107. Meraldi P, Lukas J, Fry AM, Bartek J, Nigg EA. Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin A. Nat Cell Biol 1999;1:88-93.
108. Tsou MF, Stearns T. Mechanism limiting centrosome duplication to once per cell cycle. Nature 2006;442:947-51.
109. Saavedra HI, Maiti B, Timmers C, Altura R, Tokuyama Y, Fukasawa K, Leone G. Inactivation of E2F3 results in centrosome amplification. Cancer Cell 2003;3:333-46.
110. Lee MY, Moreno CS, Saavedra HI. E2F activators signal and maintain centrosome amplification in breast cancer cells. Mol Cell Biol 2014;34:2581-99.
111. Nigg EA, Holland AJ. Once and only once: mechanisms of centriole duplication and their deregulation in disease. Nat Rev Mol Cell Biol 2018;19:297-312.
112. McLamarrah TA, Buster DW, Galletta BJ, Boese CJ, Ryniawec JM, Hollingsworth NA, Byrnes AE, Brownlee CW, Slep KC, Rusan NM, Rogers GC. An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly. J Cell Biol 2018; doi: 10.1083/jcb.201605106.
113. Dzhindzhev NS, Tzolovsky G, Lipinszki Z, Abdelaziz M, Debski J, Dadlez M, Glover DM. Two-step phosphorylation of Ana2 by Plk4 is required for the sequential loading of Ana2 and Sas6 to initiate procentriole formation. Open Biol 2017;7:170247.
114. Arquint C, Cubizolles F, Morand A, Schmidt A, Nigg EA. The SKP1-Cullin-F-box E3 ligase betaTrCP and CDK2 cooperate to control STIL abundance and centriole number. Open Biol 2018;8:170253.
115. Vulprecht J, David A, Tibelius A, Castiel A, Konotop G, Liu F, Bestvater F, Raab MS, Zentgraf H, Izraeli S, Kramer A. STIL is required for centriole duplication in human cells. J Cell Sci 2012;125:1353-62.
116. Kasbek C, Yang CH, Yusof AM, Chapman HM, Winey M, Fisk HA. Preventing the degradation of mps1 at centrosomes is sufficient to cause centrosome reduplication in human cells. Mol Biol Cell 2007;18:4457-69.
117. Cowley DO, Rivera-Perez JA, Schliekelman M, He YJ, Oliver TG, Lu L, O'Quinn R, Salmon ED, Magnuson T, Van Dyke T. Aurora-A kinase is essential for bipolar spindle formation and early development. Mol Cell Biol 2009;29:1059-71.
118. Hirota T, Kunitoku N, Sasayama T, Marumoto T, Zhang D, Nitta M, Hatakeyama K, Saya H. Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell 2003;114:585-98.
119. Kramer A, Mailand N, Lukas C, Syljuasen RG, Wilkinson CJ, Nigg EA, Bartek J, Lukas J. Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase. Nat Cell Biol 2004;6:884-91.
120. Lane HA, Nigg EA. Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol 1996;135:1701-13.
121. Mardin BR, Agircan FG, Lange C, Schiebel E. Plk1 controls the Nek2A-PP1gamma antagonism in centrosome disjunction. Curr Biol 2011;21:1145-51.
122. Spankuch-Schmitt B, Bereiter-Hahn J, Kaufmann M, Strebhardt K. Effect of RNA silencing of polo-like kinase-1 (PLK1) on apoptosis and spindle formation in human cancer cells. J Natl Cancer Inst 2002;94:1863-77.
123. Faragher AJ, Fry AM. Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles. Mol Biol Cell 2003;14:2876-89.
124. Bahmanyar S, Kaplan DD, Deluca JG, Giddings TH Jr, O'Toole ET, Winey M, Salmon ED, Casey PJ, Nelson WJ, Barth AI. beta-Catenin is a Nek2 substrate involved in centrosome separation. Genes Dev 2008;22:91-105.
125. Meraldi P, Sorger PK. A dual role for Bub1 in the spindle checkpoint and chromosome congression. EMBO J 2005;24:1621-33.
126. Dou Z, Liu X, Wang W, Zhu T, Wang X, Xu L, Abrieu A, Fu C, Hill DL, Yao X. Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment. Proc Natl Acad Sci U S A 2015;112:E4546-55.
127. Tang Z, Sun Y, Harley SE, Zou H, Yu H. Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis. Proc Natl Acad Sci U S A 2004;101:18012-7.
128. Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell 2006;10:575-85.
129. Adams RR, Carmena M, Earnshaw WC. Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol 2001;11:49-54.
130. Holland AJ, Lan W, Cleveland DW. Centriole duplication: a lesson in self-control. Cell Cycle 2010;9:2731-6.
131. Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G, Godinho SA. Centrosomes and cilia in human disease. Trends Genet 2011;27:307-15.
132. Nigg EA, Schnerch D, Ganier O. Impact of centrosome aberrations on chromosome segregation and tissue architecture in cancer. Cold Spring Harb Symp Quant Biol 2018; doi: 10.1101/sqb.2017.82.034421.
133. Lingle WL, Lutz WH, Ingle JN, Maihle NJ, Salisbury JL. Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proc Natl Acad Sci U S A 1998;95:2950-5.
134. Guo HQ, Gao M, Ma J, Xiao T, Zhao LL, Gao Y, Pan QJ. Analysis of the cellular centrosome in fine-needle aspirations of the breast. Breast Cancer Res 2007;9:R48.
135. Salisbury JL, Lingle WL, White RA, Cordes LE, Barrett S. Microtubule nucleating capacity of centrosomes in tissue sections. J Histochem Cytochem 1999;47:1265-74.
136. Lingle WL, Barrett SL, Negron VC, D'Assoro AB, Boeneman K, Liu W, Whitehead CM, Reynolds C, Salisbury JL. Centrosome amplification drives chromosomal instability in breast tumor development. Proc Natl Acad Sci U S A 2002;99:1978-83.
137. D'Assoro AB, Barrett SL, Folk C, Negron VC, Boeneman K, Busby R, Whitehead C, Stivala F, Lingle WL, Salisbury JL. Amplified centrosomes in breast cancer: a potential indicator of tumor aggressiveness. Breast Cancer Res Treat 2002;75:25-34.
138. D'Assoro AB, Lingle WL, Salisbury JL. Centrosome amplification and the development of cancer. Oncogene 2002;21:6146-53.
140. Krzywicka-Racka A, Sluder G. Repeated cleavage failure does not establish centrosome amplification in untransformed human cells. J Cell Biol 2011;194:199-207.
141. Weaver BA, Silk AD, Cleveland DW. Low rates of aneuploidy promote tumorigenesis while high rates of aneuploidy cause cell death and tumor suppression. Cell Oncol 2008;30:453.
142. Kwon M, Godinho SA, Chandhok NS, Ganem NJ, Azioune A, Thery M, Pellman D. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 2008;22:2189-203.
143. Quintyne NJ, Reing JE, Hoffelder DR, Gollin SM, Saunders WS. Spindle multipolarity is prevented by centrosomal clustering. Science 2005;307:127-9.
144. Silkworth WT, Nardi IK, Scholl LM, Cimini D. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells. PLoS One 2009;4:e6564.
145. Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT, Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 2005;437:1043-7.
146. Weaver BA, Silk AD, Montagna C, Verdier-Pinard P, Cleveland DW. Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell 2007;11:25-36.
147. Sabino D, Gogendeau D, Gambarotto D, Nano M, Pennetier C, Dingli F, Arras G, Loew D, Basto R. Moesin is a major regulator of centrosome behavior in epithelial cells with extra centrosomes. Curr Biol 2015;25:879-89.
148. Vitre B, Holland AJ, Kulukian A, Shoshani O, Hirai M, Wang Y, Maldonado M, Cho T, Boubaker J, Swing DA, Tessarollo L, Evans SM, Fuchs E, Cleveland DW. Chronic centrosome amplification without tumorigenesis. Proc Natl Acad Sci U S A 2015;112:E6321-30.
149. Marthiens V, Rujano MA, Pennetier C, Tessier S, Paul-Gilloteaux P, Basto R. Centrosome amplification causes microcephaly. Nat Cell Biol 2013;15:731-40.
150. Lee M, Oprea-Ilies G, Saavedra HI. Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis. Oncotarget 2015;6:37316-34.
151. Schneeweiss A, Sinn HP, Ehemann V, Khbeis T, Neben K, Krause U, Ho AD, Bastert G, Kramer A. Centrosomal aberrations in primary invasive breast cancer are associated with nodal status and hormone receptor expression. Int J Cancer 2003;107:346-52.
152. Denu RA, Zasadil LM, Kanugh C, Laffin J, Weaver BA, Burkard ME. Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer. BMC Cancer 2016;16:47.
153. Pannu V, Mittal K, Cantuaria G, Reid MD, Li X, Donthamsetty S, McBride M, Klimov S, Osan R, Gupta MV, Rida PC, Aneja R. Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers. Oncotarget 2015;6:10487-97.
154. Basto R, Brunk K, Vinadogrova T, Peel N, Franz A, Khodjakov A, Raff JW. Centrosome amplification can initiate tumorigenesis in flies. Cell 2008;133:1032-42.
155. Castellanos E, Dominguez P, Gonzalez C. Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol 2008;18:1209-14.
156. Suizu F, Ryo A, Wulf G, Lim J, Lu KP. Pin1 regulates centrosome duplication, and its overexpression induces centrosome amplification, chromosome instability, and oncogenesis. Mol Cell Biol 2006;26:1463-79.
157. Wang X, Zhou YX, Qiao W, Tominaga Y, Ouchi M, Ouchi T, Deng CX. Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene 2006;25:7148-58.
158. Coelho PA, Bury L, Shahbazi MN, Liakath-Ali K, Tate PH, Wormald S, Hindley CJ, Huch M, Archer J, Skarnes WC, Zernicka-Goetz M, Glover DM. Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse. Open Biol 2015;5:150209.
159. Sercin O, Larsimont JC, Karambelas AE, Marthiens V, Moers V, Boeckx B, Le Mercier M, Lambrechts D, Basto R, Blanpain C. Transient PLK4 overexpression accelerates tumorigenesis in p53-deficient epidermis. Nat Cell Biol 2016;18:100-10.
160. Levine MS, Bakker B, Boeckx B, Moyett J, Lu J, Vitre B, Spierings DC, Lansdorp PM, Cleveland DW, Lambrechts D, Foijer F, Holland AJ. Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals. Dev Cell 2017;40:313-22.e5.
161. Godinho SA, Picone R, Burute M, Dagher R, Su Y, Leung CT, Polyak K, Brugge JS, Thery M, Pellman D. Oncogene-like induction of cellular invasion from centrosome amplification. Nature 2014;510:167-71.
162. Lee M, Oprea-Ilies G, Saavedra HI. Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis. Oncotarget 2015;6:37316-34.
163. Schnerch D, Nigg EA. Structural centrosome aberrations favor proliferation by abrogating microtubule-dependent tissue integrity of breast epithelial mammospheres. Oncogene 2016;35:2711-22.
164. Casenghi M, Meraldi P, Weinhart U, Duncan PI, Korner R, Nigg EA. Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation. Dev Cell 2003;5:113-25.
165. Shao S, Liu R, Wang Y, Song Y, Zuo L, Xue L, Lu N, Hou N, Wang M, Yang X, Zhan Q. Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice. J Clin Invest 2010;120:498-507.
166. Yu L, Song Y, Zhang Q, Zhan Q. Ninein-like protein is overexpressed in head and neck squamous cell carcinoma and contributes to cancer growth and resistance to apoptosis. Oncol Rep 2009;22:789-98.
167. Qu D, Qu H, Fu M, Zhao X, Liu R, Sui L, Zhan Q. Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis. Gynecol Oncol 2008;110:230-6.
168. Ganier O, Schnerch D, Oertle P, Lim RY, Plodinec M, Nigg EA. Structural centrosome aberrations promote non-cell-autonomous invasiveness. EMBO J 2018;37:e98576.
169. Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF. Abnormal centrosome amplification in the absence of p53. Science 1996;271:1744-7.
170. Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C, van Es JH, Breukel C, Wiegant J, Giles RH, Clevers H. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 2001;3:433-8.
171. Tutt A, Gabriel A, Bertwistle D, Connor F, Paterson H, Peacock J, Ross G, Ashworth A. Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification. Curr Biol 1999;9:1107-10.
172. Wang X, Wang RH, Li W, Xu X, Hollander MC, Fornace AJ Jr, Deng CX. Genetic interactions between Brca1 and Gadd45a in centrosome duplication, genetic stability, and neural tube closure. J Biol Chem 2004;279:29606-14.
173. Ishida S, Huang E, Zuzan H, Spang R, Leone G, West M, Nevins JR. Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis. Mol Cell Biol 2001;21:4684-99.
174. Harrison Pitner MK, Saavedra HI. Cdk4 and nek2 signal binucleation and centrosome amplification in a her2+ breast cancer model. PLoS One 2013;8:e65971.
175. Leontovich AA, Salisbury JL, Veroux M, Tallarita T, Billadeau D, McCubrey J, Ingle J, Galanis E, D'Assoro AB. Inhibition of Cdk2 activity decreases Aurora-A kinase centrosomal localization and prevents centrosome amplification in breast cancer cells. Oncol Rep 2013;29:1785-8.
176. Leone G, DeGregori J, Sears R, Jakoi L, Nevins JR. Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F. Nature 1997;387:422-6.
177. Iovino F, Lentini L, Amato A, Di Leonardo A. RB acute loss induces centrosome amplification and aneuploidy in murine primary fibroblasts. Mol Cancer 2006;5:38.
178. Chen HZ, Tsai SY, Leone G. Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer 2009;9:785-97.
179. Kuznetsova AY, Seget K, Moeller GK, de Pagter MS, de Roos JA, Durrbaum M, Kuffer C, Muller S, Zaman GJ, Kloosterman WP, Storchova Z. Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. Cell Cycle 2015;14:2810-20.
180. Sotillo R, Schvartzman JM, Socci ND, Benezra R. Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. Nature 2010;464:436-40.
181. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S, Tuveson DA. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005;7:469-83.
182. McCreery MQ, Halliwill KD, Chin D, Delrosario R, Hirst G, Vuong P, Jen KY, Hewinson J, Adams DJ, Balmain A. Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers. Nat Med 2015;21:1514-20.
183. Duesberg P, Li R, Sachs R, Fabarius A, Upender MB, Hehlmann R. Cancer drug resistance: the central role of the karyotype. Drug Resist Updat 2007;10:51-8.
184. McGranahan N, Burrell RA, Endesfelder D, Novelli MR, Swanton C. Cancer chromosomal instability: therapeutic and diagnostic challenges. EMBO Rep 2012;13:528-38.
185. Shapiro JR, Mehta BM, Ebrahim SA, Scheck AC, Moots PL, Fiola MR. Tumor heterogeneity and intrinsically chemoresistant subpopulations in freshly resected human malignant gliomas. Basic Life Sci 1991;57:243-61; discussion 261.
186. Zhou YH, Chen Y, Hu Y, Yu L, Tran K, Giedzinski E, Ru N, Gau A, Pan F, Qiao J, Atkin N, Ly KC, Lee N, Siegel ER, Linskey ME, Wang P, Limoli C. The role of EGFR double minutes in modulating the response of malignant gliomas to radiotherapy. Oncotarget 2017;8:80853-68.
187. Hu Y, Ru N, Xiao H, Chaturbedi A, Hoa NT, Tian XJ, Zhang H, Ke C, Yan F, Nelson J, Li Z, Gramer R, Yu L, Siegel E, Zhang X, Jia Z, Jadus MR, Limoli CL, Linskey ME, Xing J, Zhou YH. Tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity. PLoS One 2013;8:e80898.
188. Heerema NA, Sather HN, Sensel MG, Zhang T, Hutchinson RJ, Nachman JB, Lange BJ, Steinherz PG, Bostrom BC, Reaman GH, Gaynon PS, Uckun FM. Prognostic impact of trisomies of chromosomes 10, 17, and 5 among children with acute lymphoblastic leukemia and high hyperdiploidy (> 50 chromosomes). J Clin Oncol 2000;18:1876-87.
189. Rivera-Rivera Y, Saavedra HI. Centrosome - a promising anti-cancer target. Biologics 2016;10:167-76.
190. Marina M, Saavedra HI. Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance. Front Biosci (Landmark Ed) 2014;19:352-65.
191. Finn RS, Aleshin A, Slamon DJ. Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. Breast Cancer Res 2016;18:17.
192. Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015;16:25-35.
193. Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res 2009;11:R77.
194. Dean JL, Thangavel C, McClendon AK, Reed CA, Knudsen ES. Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure. Oncogene 2010;29:4018-32.
195. Goldberg SL, Fenaux P, Craig MD, Gyan E, Lister J, Kassis J, Pigneux A, Schiller GJ, Jung J, Jane Leonard E, Fingert H, Westervelt P. An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes. Leuk Res Rep 2014;3:58-61.
196. Komarova NL, Wodarz D. The optimal rate of chromosome loss for the inactivation of tumor suppressor genes in cancer. Proc Natl Acad Sci U S A 2004;101:7017-21.
197. Weaver BA, Cleveland DW. Aneuploidy: instigator and inhibitor of tumorigenesis. Cancer Res 2007;67:10103-5.
198. Jamal-Hanjani M, A'Hern R, Birkbak NJ, Gorman P, Gronroos E, Ngang S, Nicola P, Rahman L, Thanopoulou E, Kelly G, Ellis P, Barrett-Lee P, Johnston SR, Bliss J, Roylance R, Swanton C. Extreme chromosomal instability forecasts improved outcome in ER-negative breast cancer: a prospective validation cohort study from the TACT trial. Ann Oncol 2015;26:1340-6.
199. Janssen A, Kops GJ, Medema RH. Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells. Proc Natl Acad Sci U S A 2009;106:19108-13.
200. Shackney SE, Silverman JF. Molecular evolutionary patterns in breast cancer. Adv Anat Pathol 2003;10:278-90.
201. Lee HS, Lee NC, Kouprina N, Kim JH, Kagansky A, Bates S, Trepel JB, Pommier Y, Sackett D, Larionov V. Effects of anticancer drugs on chromosome instability and new clinical implications for tumor-suppressing therapies. Cancer Res 2016;76:902-11.