The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment

Cell

Volumn 174, Issue 6, 2018, Pages 1347-1360

  Bakhoum, Samuel F ^a   Cantley, Lewis C ^b  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOUBLE STRANDED DNA; INTERFERON; MEMBRANE PROTEIN; MPYS PROTEIN, HUMAN; NUCLEOTIDYLTRANSFERASE;

ANEUPLOIDY; CANCER CELL; CHROMOSOMAL INSTABILITY; CHROMOSOME SEGREGATION; CYTOSOL; GENETIC HETEROGENEITY; HUMAN; INNATE IMMUNITY; MALIGNANT NEOPLASM; METASTASIS; MITOSIS; NATURAL SELECTION; NONHUMAN; PRIORITY JOURNAL; PROGNOSIS; REVIEW; SIGNAL TRANSDUCTION; TUMOR ESCAPE; TUMOR MICROENVIRONMENT; IMMUNOLOGY; METABOLISM; NEOPLASM; PATHOLOGY;

ANEUPLOIDY; CHROMOSOMAL INSTABILITY; HUMANS; IMMUNITY, INNATE; INTERFERON TYPE I; MEMBRANE PROTEINS; NEOPLASMS; NUCLEOTIDYLTRANSFERASES; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

EID: 85052746903     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2018.08.027     Document Type: Review

References (114)

1. Abe, T., Barber, G.N., Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-κB activation through TBK1. J. Virol. 88 (2014), 5328–5341.
2. Ahn, J., Xia, T., Konno, H., Konno, K., Ruiz, P., Barber, G.N., Inflammation-driven carcinogenesis is mediated through STING. Nat. Commun., 5, 2014, 5166.
3. Baird, J.R., Friedman, D., Cottam, B., Dubensky, T.W. Jr., Kanne, D.B., Bambina, S., Bahjat, K., Crittenden, M.R., Gough, M.J., Radiotherapy Combined with Novel STING-Targeting Oligonucleotides Results in Regression of Established Tumors. Cancer Res. 76 (2016), 50–61.
4. Bakhoum, S.F., Danilova, O.V., Kaur, P., Levy, N.B., Compton, D.A., Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma. Clin. Cancer Res. 17 (2011), 7704–7711.
5. Bakhoum, S.F., Kabeche, L., Murnane, J.P., Zaki, B.I., Compton, D.A., DNA-damage response during mitosis induces whole-chromosome missegregation. Cancer Discov. 4 (2014), 1281–1289.
6. Bakhoum, S.F., Kabeche, L., Wood, M.D., Laucius, C.D., Qu, D., Laughney, A.M., Reynolds, G.E., Louie, R.J., Phillips, J., Chan, D.A., et al. Numerical chromosomal instability mediates susceptibility to radiation treatment. Nat. Commun., 6, 2015, 5990.
7. Bakhoum, S.F., Ngo, B., Laughney, A.M., Cavallo, J.-A., Murphy, C.J., Ly, P., Shah, P., Sriram, R.K., Watkins, T.B.K., Taunk, N.K., et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 553 (2018), 467–472.
8. Bakker, B., Taudt, A., Belderbos, M.E., Porubsky, D., Spierings, D.C., de Jong, T.V., Halsema, N., Kazemier, H.G., Hoekstra-Wakker, K., Bradley, A., et al. Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies. Genome Biol., 17, 2016, 115.
9. Bielski, C.M., Zehir, A., Penson, A.V., Donoghue, M.T.A., Chatila, W., Armenia, J., Chang, M.T., Schram, A.M., Jonsson, P., Bandlamudi, C., et al. Genome doubling shapes the evolution and prognosis of advanced cancers. Nat. Genet. 50 (2018), 1189–1195.
10. Birkbak, N.J., Eklund, A.C., Li, Q., McClelland, S.E., Endesfelder, D., Tan, P., Tan, I.B., Richardson, A.L., Szallasi, Z., Swanton, C., Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res. 71 (2011), 3447–3452.
11. Boveri, T. (1914). Zur Frage der Entstehung maligner Tumoren.
12. Burkard, M.E., Weaver, B.A., Tuning Chromosomal Instability to Optimize Tumor Fitness. Cancer Discov. 7 (2017), 134–136.
13. Cai, X., Chiu, Y.-H., Chen, Z.J., The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. Mol. Cell 54 (2014), 289–296.
14. Campbell, P.J., Yachida, S., Mudie, L.J., Stephens, P.J., Pleasance, E.D., Stebbings, L.A., Morsberger, L.A., Latimer, C., McLaren, S., Lin, M.-L., et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467 (2010), 1109–1113.
15. Cañadas, I., Thummalapalli, R., Kim, J.W., Kitajima, S., Jenkins, R.W., Christensen, C.L., Campisi, M., Kuang, Y., Zhang, Y., Gjini, E., et al. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat. Med. 24 (2018), 1143–1150.
16. Carter, S.L.S., Cibulskis, K., Helman, E., McKenna, A., Shen, H., Zack, T., Laird, P.W., Onofrio, R.C., Winckler, W., Weir, B.A., et al. Absolute quantification of somatic DNA alterations in human cancer. Nat. Biotechnol. 30 (2012), 413–421.
17. Carter, S.L., Eklund, A.C., Kohane, I.S., Harris, L.N., Szallasi, Z., A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat. Genet. 38 (2006), 1043–1048.
18. Cerboni, S., Jeremiah, N., Gentili, M., Gehrmann, U., Conrad, C., Stolzenberg, M.-C., Picard, C., Neven, B., Fischer, A., Amigorena, S., et al. Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes. J. Exp. Med. 214 (2017), 1769–1785.
19. Chandra, D., Quispe-Tintaya, W., Jahangir, A., Asafu-Adjei, D., Ramos, I., Sintim, H.O., Zhou, J., Hayakawa, Y., Karaolis, D.K.R., Gravekamp, C., STING ligand c-di-GMP improves cancer vaccination against metastatic breast cancer. Cancer Immunol. Res. 2 (2014), 901–910.
20. Chen, G., Bradford, W.D., Seidel, C.W., Li, R., Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. Nature 482 (2012), 246–250.
21. Chen, Y., Wang, L., Jin, J., Luan, Y., Chen, C., Li, Y., Chu, H., Wang, X., Liao, G., Yu, Y., et al. p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation. J. Exp. Med. 214 (2017), 991–1010.
22. Chowell, D., Morris, L.G.T., Grigg, C.M., Weber, J.K., Samstein, R.M., Makarov, V., Kuo, F., Kendall, S.M., Requena, D., Riaz, N., et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 359 (2018), 582–587.
23. Cimini, D., Merotelic kinetochore orientation, aneuploidy, and cancer. Biochim. Biophys. Acta 1786 (2008), 32–40.
24. Cimini, D., Howell, B., Maddox, P., Khodjakov, A., Degrassi, F., Salmon, E.D., Merotelic kinetochore orientation is a major mechanism of aneuploidy in mitotic mammalian tissue cells. J. Cell Biol. 153 (2001), 517–527.
25. Comaills, V., Kabeche, L., Morris, R., Buisson, R., Yu, M., Madden, M.W., LiCausi, J.A., Boukhali, M., Tajima, K., Pan, S., et al. Genomic instability is induced by persistent proliferation of cells undergoing epithelial-to-mesenchymal transition. Cell Rep. 17 (2016), 2632–2647.
26. Coquel, F., Silva, M.-J., Técher, H., Zadorozhny, K., Sharma, S., Nieminuszczy, J., Mettling, C., Dardillac, E., Barthe, A., Schmitz, A.-L., et al. SAMHD1 acts at stalled replication forks to prevent interferon induction. Nature 557 (2018), 57–61.
27. Coussens, L.M., Werb, Z., Inflammation and cancer. Nature 420 (2002), 860–867.
28. Crasta, K., Ganem, N.J., Dagher, R., Lantermann, A.B., Ivanova, E.V., Pan, Y., Nezi, L., Protopopov, A., Chowdhury, D., Pellman, D., DNA breaks and chromosome pulverization from errors in mitosis. Nature 482 (2012), 53–58.
29. Crow, Y.J., Hayward, B.E., Parmar, R., Robins, P., Leitch, A., Ali, M., Black, D.N., van Bokhoven, H., Brunner, H.G., Hamel, B.C., et al. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nat. Genet. 38 (2006), 917–920.
30. Davoli, T., Uno, H., Wooten, E.C., Elledge, S.J., Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science, 355, 2017.
31. Davoli, T., Xu, A.W., Mengwasser, K.E., Sack, L.M., Yoon, J.C., Park, P.J., Elledge, S.J., Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome. Cell 155 (2013), 948–962.
32. Denais, C.M., Gilbert, R.M., Isermann, P., McGregor, A.L., te Lindert, M., Weigelin, B., Davidson, P.M., Friedl, P., Wolf, K., Lammerding, J., Nuclear envelope rupture and repair during cancer cell migration. Science 352 (2016), 353–358.
33. Dou, Z., Ghosh, K., Vizioli, M.G., Zhu, J., Sen, P., Wangensteen, K.J., Simithy, J., Lan, Y., Lin, Y., Zhou, Z., et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature 550 (2017), 402–406.
34. Galluzzi, L., Vanpouille-Box, C., Bakhoum, S.F., Demaria, S., SnapShot: CGAS-STING Signaling. Cell 173 (2018), 276–276.e1.
35. Gaston, J., Cheradame, L., Yvonnet, V., Deas, O., Poupon, M.-F., Judde, J.-G., Cairo, S., Goffin, V., Intracellular STING inactivation sensitizes breast cancer cells to genotoxic agents. Oncotarget 7 (2016), 77205–77224.
36. Glück, S., Guey, B., Gulen, M.F., Wolter, K., Kang, T.-W., Schmacke, N.A., Bridgeman, A., Rehwinkel, J., Zender, L., Ablasser, A., Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence. Nat. Cell Biol. 19 (2017), 1061–1070.
37. Goh, J.Y., Feng, M., Wang, W., Oguz, G., Yatim, S.M.J.M., Lee, P.L., Bao, Y., Lim, T.H., Wang, P., Tam, W.L., et al. Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence. Nat. Med. 23 (2017), 1319–1330.
38. Graham, N.A., Minasyan, A., Lomova, A., Cass, A., Balanis, N.G., Friedman, M., Chan, S., Zhao, S., Delgado, A., Go, J., et al. Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures. Mol. Syst. Biol., 13, 2017, 914.
39. Gulen, M.F., Koch, U., Haag, S.M., Schuler, F., Apetoh, L., Villunger, A., Radtke, F., Ablasser, A., Signalling strength determines proapoptotic functions of STING. Nat. Commun., 8, 2017, 427.
40. Gutenberg, A., Gerdes, J.S., Jung, K., Sander, B., Gunawan, B., Bock, H.C., Liersch, T., Brück, W., Rohde, V., Füzesi, L., High chromosomal instability in brain metastases of colorectal carcinoma. Cancer Genet. Cytogenet. 198 (2010), 47–51.
41. Harding, S.M., Benci, J.L., Irianto, J., Discher, D.E., Minn, A.J., Greenberg, R.A., Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548 (2017), 466–470.
42. Hatch, E.M., Fischer, A.H., Deerinck, T.J., Hetzer, M.W., Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 154 (2013), 47–60.
43. Herrtwich, L., Nanda, I., Evangelou, K., Nikolova, T., Horn, V., Sagar, Erny, D., Stefanowski, J., Rogell, L., Klein, C., et al. DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas. Cell 167 (2016), 1264–1280.e18.
44. Heyman, M., Grandér, D., Bröndum-Nielsen, K., Liu, Y., Söderhäll, S., Einhorn, S., Deletions of the short arm of chromosome 9, including the interferon-alpha/-beta genes, in acute lymphocytic leukemia. Studies on loss of heterozygosity, parental origin of deleted genes and prognosis. Int. J. Cancer 54 (1993), 748–753.
45. Ho, S.S.W., Zhang, W.Y.L., Tan, N.Y.J., Khatoo, M., Suter, M.A., Tripathi, S., Cheung, F.S.G., Lim, W.K., Tan, P.H., Ngeow, J., Gasser, S., The DNA Structure-Specific Endonuclease MUS81 Mediates DNA Sensor STING-Dependent Host Rejection of Prostate Cancer Cells. Immunity 44 (2016), 1177–1189.
46. Ishikawa, H., Barber, G.N., STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455 (2008), 674–678.
47. Ishikawa, H., Ma, Z., Barber, G.N., STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461 (2009), 788–792.
48. Jamal-Hanjani, M., A'Hern, R., Birkbak, N.J., Gorman, P., Grönroos, E., Ngang, S., Nicola, P., Rahman, L., Thanopoulou, E., Kelly, G., et al. Extreme chromosomal instability forecasts improved outcome in ER-negative breast cancer: a prospective validation cohort study from the TACT trial. Ann. Oncol. 26 (2015), 1340–1346.
49. Jamal-Hanjani, M., Wilson, G.A., McGranahan, N., Birkbak, N.J., Watkins, T.B.K., Veeriah, S., Shafi, S., Johnson, D.H., Mitter, R., Rosenthal, R., et al., TRACERx Consortium. Tracking the Evolution of Non-Small-Cell Lung Cancer. N. Engl. J. Med. 376 (2017), 2109–2121.
50. Karagiannis, G.S., Pastoriza, J.M., Wang, Y., Harney, A.S., Entenberg, D., Pignatelli, J., Sharma, V.P., Xue, E.A., Cheng, E., D'Alfonso, T.M., et al. Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Sci. Transl. Med., 9, 2017.
51. Kato, H., Sandberg, A.A., Chromosome pulverization in human cells with micronuclei. J. Natl. Cancer Inst. 40 (1968), 165–179.
52. Kis-Toth, K., Szanto, A., Thai, T.H., Tsokos, G.C., Cytosolic DNA-activated human dendritic cells are potent activators of the adaptive immune response. J. Immunol. 187 (2011), 1222–1234.
53. Konno, H., Yamauchi, S., Berglund, A., Putney, R.M., Mulé, J.J., Barber, G.N., Suppression of STING signaling through epigenetic silencing and missense mutation impedes DNA damage mediated cytokine production. Oncogene 37 (2018), 2037–2051.
54. Lam, A.R., Bert, N.L., Ho, S.S., Shen, Y.J., Tang, L.F., Xiong, G.M., Croxford, J.L., Koo, C.X., Ishii, K.J., Akira, S., et al. RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor pathways in lymphoma. Cancer Res. 74 (2014), 2193–2203.
55. Lau, L., Gray, E.E., Brunette, R.L., Stetson, D.B., DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway. Science 350 (2015), 568–571.
56. Laughney, A.M., Elizalde, S., Genovese, G., Bakhoum, S.F., Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution. Cell Rep. 12 (2015), 809–820.
57. Lee, H.-S., Lee, N.C.O., Kouprina, N., Kim, J.-H., Kagansky, A., Bates, S., Trepel, J.B., Pommier, Y., Sackett, D., Larionov, V., Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies. Cancer Res. 76 (2016), 902–911.
58. Lee-Kirsch, M.A., Gong, M., Chowdhury, D., Senenko, L., Engel, K., Lee, Y.-A., de Silva, U., Bailey, S.L., Witte, T., Vyse, T.J., et al. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat. Genet. 39 (2007), 1065–1067.
59. Lengauer, C., Kinzler, K.W., Vogelstein, B., Genetic instabilities in human cancers. Nature 396 (1998), 643–649.
60. Lengauer, C., Kinzler, K.W., Vogelstein, B., Genetic instability in colorectal cancers. Nature 386 (1997), 623–627.
61. Li, Q., Ma, Z., Liu, Y., Kan, X., Wang, C., Su, B., Li, Y., Zhang, Y., Wang, P., Luo, Y., et al. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model. FEBS J. 283 (2016), 2836–2852.
62. Liang, D., Xiao-Feng, H., Guan-Jun, D., Er-Ling, H., Sheng, C., Ting-Ting, W., Qin-Gang, H., Yan-Hong, N., Ya-Yi, H., Activated STING enhances Tregs infiltration in the HPV-related carcinogenesis of tongue squamous cells via the c-jun/CCL22 signal. Biochim. Biophys. Acta 1852 (2015), 2494–2503.
63. Liang, H., Deng, L., Hou, Y., Meng, X., Huang, X., Rao, E., Zheng, W., Mauceri, H., Mack, M., Xu, M., et al. Host STING-dependent MDSC mobilization drives extrinsic radiation resistance. Nat. Commun., 8, 2017, 1736.
64. Linsley, P.S., Speake, C., Whalen, E., Chaussabel, D., Copy number loss of the interferon gene cluster in melanomas is linked to reduced T cell infiltrate and poor patient prognosis. PLoS ONE, 9, 2014, e109760.
65. Litvin, O., Schwartz, S., Wan, Z., Schild, T., Rocco, M., Oh, N.L., Chen, B.-J., Goddard, N., Pratilas, C., Pe'er, D., Interferon α/β Enhances the Cytotoxic Response of MEK Inhibition in Melanoma. Mol. Cell 57 (2015), 784–796.
66. Loh, P.-R., Genovese, G., Handsaker, R.E., Finucane, H.K., Reshef, Y.A., Palamara, P.F., Birmann, B.M., Talkowski, M.E., Bakhoum, S.F., McCarroll, S.A., Price, A.L., Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature 559 (2018), 350–355.
67. Ly, P., Teitz, L.S., Kim, D.H., Shoshani, O., Skaletsky, H., Fachinetti, D., Page, D.C., Cleveland, D.W., Selective Y centromere inactivation triggers chromosome shattering in micronuclei and repair by non-homologous end joining. Nat. Cell Biol. 19 (2017), 68–75.
68. Maciejowski, J., Li, Y., Bosco, N., Campbell, P.J., de Lange, T., Chromothripsis and Kataegis Induced by Telomere Crisis. Cell 163 (2015), 1641–1654.
69. Mackenzie, K.J., Carroll, P., Martin, C.-A., Murina, O., Fluteau, A., Simpson, D.J., Olova, N., Sutcliffe, H., Rainger, J.K., Leitch, A., et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature 548 (2017), 461–465.
70. McGranahan, N., Rosenthal, R., Hiley, C.T., Rowan, A.J., Watkins, T.B.K., Wilson, G.A., Birkbak, N.J., Veeriah, S., Van Loo, P., Herrero, J., Swanton, C., TRACERx Consortium. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution. Cell 171 (2017), 1259–1271.e11.
71. Mueller, S., Engleitner, T., Maresch, R., Zukowska, M., Lange, S., Kaltenbacher, T., Konukiewitz, B., Öllinger, R., Zwiebel, M., Strong, A., et al. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. Nature 554 (2018), 62–68.
72. Notta, F., Chan-Seng-Yue, M., Lemire, M., Li, Y., Wilson, G.W., Connor, A.A., Denroche, R.E., Liang, S.-B., Brown, A.M.K., Kim, J.C., et al. A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature 538 (2016), 378–382.
73. Pailler, E., Auger, N., Lindsay, C.R., Vielh, P., Islas-Morris-Hernandez, A., Borget, I., Ngo-Camus, M., Planchard, D., Soria, J.-C., Besse, B., Farace, F., High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer. Ann. Oncol. 26 (2015), 1408–1415.
74. Paulsson, K., Johansson, B., Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes. Pathol. Biol. (Paris) 55 (2007), 37–48.
75. Pavelka, N., Rancati, G., Zhu, J., Bradford, W.D., Saraf, A., Florens, L., Sanderson, B.W., Hattem, G.L., Li, R., Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 468 (2010), 321–325.
76. Potapova, T.A., Zhu, J., Li, R., Aneuploidy and chromosomal instability: a vicious cycle driving cellular evolution and cancer genome chaos. Cancer Metastasis Rev. 32 (2013), 377–389.
77. Rowald, K., Mantovan, M., Passos, J., Buccitelli, C., Mardin, B.R., Korbel, J.O., Jechlinger, M., Sotillo, R., Negative selection and chromosome instability induced by Mad2 overexpression delay breast cancer but facilitate oncogene-independent outgrowth. Cell Rep. 15 (2016), 2679–2691.
78. Roylance, R., Endesfelder, D., Gorman, P., Burrell, R.A., Sander, J., Tomlinson, I., Hanby, A.M., Speirs, V., Richardson, A.L., Birkbak, N.J., et al. Relationship of extreme chromosomal instability with long-term survival in a retrospective analysis of primary breast cancer. Cancer Epidemiol. Biomarkers Prev. 20 (2011), 2183–2194.
79. Sack, L.M., Davoli, T., Li, M.Z., Li, Y., Xu, Q., Naxerova, K., Wooten, E.C., Bernardi, R.J., Martin, T.D., Chen, T., et al. Profound tissue specificity in proliferation control underlies cancer drivers and aneuploidy patterns. Cell 173 (2018), 499–514.e23.
80. Santaguida, S., Richardson, A., Iyer, D.R., M'Saad, O., Zasadil, L., Knouse, K.A., Wong, Y.L., Rhind, N., Desai, A., Amon, A., Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System. Dev. Cell 41 (2017), 638–651.e5.
81. Schoonen, P.M., Talens, F., Stok, C., Gogola, E., Heijink, A.M., Bouwman, P., Foijer, F., Tarsounas, M., Blatter, S., Jonkers, J., et al. Progression through mitosis promotes PARP inhibitor-induced cytotoxicity in homologous recombination-deficient cancer cells. Nat. Commun., 8, 2017, 15981.
82. Senovilla, L., Vitale, I., Martins, I., Tailler, M., Pailleret, C., Michaud, M., Galluzzi, L., Adjemian, S., Kepp, O., Niso-Santano, M., et al. An immunosurveillance mechanism controls cancer cell ploidy. Science 337 (2012), 1678–1684.
83. Sheltzer, J.M., Ko, J.H., Replogle, J.M., Habibe Burgos, N.C., Chung, E.S., Meehl, C.M., Sayles, N.M., Passerini, V., Storchova, Z., Amon, A., Single-chromosome Gains Commonly Function as Tumor Suppressors. Cancer Cell 31 (2017), 240–255.
84. Shen, J., PARPi triggers STING-dependent immune response and enhances therapeutic efficacy of immune checkpoint blockade independent of BRCAness. bioRxiv, 2018, 10.1101/318980.
85. Song, S., Peng, P., Tang, Z., Zhao, J., Wu, W., Li, H., Shao, M., Li, L., Yang, C., Duan, F., et al. Decreased expression of STING predicts poor prognosis in patients with gastric cancer. Sci. Rep., 7, 2017, 39858.
86. Sotillo, R., Schvartzman, J.-M., Socci, N.D., Benezra, R., Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. Nature 464 (2010), 436–440.
87. Stephens, P.J., Greenman, C.D., Fu, B., Yang, F., Bignell, G.R., Mudie, L.J., Pleasance, E.D., Lau, K.W., Beare, D., Stebbings, L.A., et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144 (2011), 27–40.
88. Stetson, D.B., Ko, J.S., Heidmann, T., Medzhitov, R., Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134 (2008), 587–598.
89. Suarez-Carmona, M., Lesage, J., Cataldo, D., Gilles, C., EMT and inflammation: inseparable actors of cancer progression. Mol. Oncol. 11 (2017), 805–823.
90. Sun, L., Wu, J., Du, F., Chen, X., Chen, Z.J., Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339 (2013), 786–791.
91. Sun, S.-C., Non-canonical NF-κB signaling pathway. Cell Res. 21 (2011), 71–85.
92. Swanton, C., Nicke, B., Schuett, M., Eklund, A.C., Ng, C., Li, Q., Hardcastle, T., Lee, A., Roy, R., East, P., et al. Chromosomal instability determines taxane response. Proc. Natl. Acad. Sci. USA 106 (2009), 8671–8676.
93. Takahashi, A., Loo, T.M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G.N., et al. Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells. Nat. Commun., 9, 2018, 1249.
94. Takashima, K., Takeda, Y., Oshiumi, H., Shime, H., Okabe, M., Ikawa, M., Matsumoto, M., Seya, T., STING in tumor and host cells cooperatively work for NK cell-mediated tumor growth retardation. Biochem. Biophys. Res. Commun. 478 (2016), 1764–1771.
95. Tang, C.-H.A., Zundell, J.A., Ranatunga, S., Lin, C., Nefedova, Y., Del Valle, J.R., Hu, C.-C.A., Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells. Cancer Res. 76 (2016), 2137–2152.
96. Tavassoli, M., Ruhrberg, C., Beaumont, V., Reynolds, K., Kirkham, N., Collins, W.P., Farzaneh, F., Whole chromosome 17 loss in ovarian cancer. Genes Chromosomes Cancer 8 (1993), 195–198.
97. Taylor, A.M., Shih, J., Ha, G., Gao, G.F., Zhang, X., Berger, A.C., Schumacher, S.E., Wang, C., Hu, H., Liu, J., et al., Cancer Genome Atlas Research Network. Genomic and Functional Approaches to Understanding Cancer Aneuploidy. Cancer Cell 33 (2018), 676–689.e3.
98. Thompson, S.L., Bakhoum, S.F., Compton, D.A., Mechanisms of chromosomal instability. Curr. Biol. 20 (2010), R285–R295.
99. Thompson, S.L., Compton, D.A., Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J. Cell Biol. 188 (2010), 369–381.
100. Thorsson, V., Gibbs, D.L., Brown, S.D., Wolf, D., Bortone, D.S., Ou Yang, T.-H., Porta-Pardo, E., Gao, G.F., Plaisier, C.L., Eddy, J.A., et al., Cancer Genome Atlas Research Network. The immune landscape of cancer. Immunity 48 (2018), 812–830.e14.
101. Torres, E.M., Sokolsky, T., Tucker, C.M., Chan, L.Y., Boselli, M., Dunham, M.J., Amon, A., Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317 (2007), 916–924.
102. Turajlic, S., Xu, H., Litchfield, K., Rowan, A., Chambers, T., Lopez, J.I., Nicol, D., O'Brien, T., Larkin, J., Horswell, S., et al. PEACE, TRACERx Renal Consortium. Tracking cancer evolution reveals constrained routes to metastases: TRACERx Renal. Cell 173 (2018), 581–594.e12.
103. Turner, K.M., Deshpande, V., Beyter, D., Koga, T., Rusert, J., Lee, C., Li, B., Arden, K., Ren, B., Nathanson, D.A., et al. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature 543 (2017), 122–125.
104. Vanpouille-Box, C., Alard, A., Aryankalayil, M.J., Sarfraz, Y., Diamond, J.M., Schneider, R.J., Inghirami, G., Coleman, C.N., Formenti, S.C., Demaria, S., DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat. Commun., 8, 2017, 15618.
105. Vogel, C.F.A., Wu, D., Goth, S.R., Baek, J., Lollies, A., Domhardt, R., Grindel, A., Pessah, I.N., Aryl hydrocarbon receptor signaling regulates NF-κB RelB activation during dendritic-cell differentiation. Immunol. Cell Biol. 91 (2013), 568–575.
106. Warth, A., Herpel, E., Krysa, S., Hoffmann, H., Schnabel, P.A., Schirmacher, P., Mechtersheimer, G., Bläker, H., Chromosomal instability is more frequent in metastasized than in non-metastasized pulmonary carcinoids but is not a reliable predictor of metastatic potential. Exp. Mol. Med. 41 (2009), 349–353.
107. Xia, T., Konno, H., Barber, G.N., Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis. Cancer Res. 76 (2016), 6747–6759.
108. Xia, T., Konno, H., Ahn, J., Barber, G.N., Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis. Cell Rep. 14 (2016), 282–297.
109. Yang, H., Wang, H., Ren, J., Chen, Q., Chen, Z.J., cGAS is essential for cellular senescence. Proc. Natl. Acad. Sci. USA 114 (2017), E4612–E4620.
110. Yates, L.R., Campbell, P.J., Evolution of the cancer genome. Nat. Rev. Genet. 13 (2012), 795–806.
111. Zaki, B.I., Suriawinata, A.A., Eastman, A.R., Garner, K.M., Bakhoum, S.F., Chromosomal instability portends superior response of rectal adenocarcinoma to chemoradiation therapy. Cancer 120 (2014), 1733–1742.
112. Zhang, A.W., McPherson, A., Milne, K., Kroeger, D.R., Hamilton, P.T., Miranda, A., Funnell, T., Little, N., de Souza, C.P.E., Laan, S., et al. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. Cell 173 (2018), 1755–1769.e22.
113. Zhang, C.-Z., Spektor, A., Cornils, H., Francis, J.M., Jackson, E.K., Liu, S., Meyerson, M., Pellman, D., Chromothripsis from DNA damage in micronuclei. Nature 522 (2015), 179–184.
114. Zierhut, C., Funabiki, H., The cytoplasmic DNA sensor cGAS promotes mitotic cell death. bioRxiv, 2017, 10.1101/168070.