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Aneuploidy and Heterogeneity Mechanisms in Human Colorectal Tumor Progression

  • Chapter
Genomic Instability and Immortality in Cancer

Part of the book series: Pezcoller Foundation Symposia ((PFSO,volume 8))

Abstract

Loss of integrity and cumulative changes in the cellular genome is a hallmark of the multistep process of cancer which progressively leads to uncontrolled cell growth and metastasis (1–3). Genome loss of integrity, genome instability, structural and numerical chromosome aberrations, and aneuploidy are interchangeable concepts and related experimental parameters. They are probably connected to one of the historic hallmarks of cancer (back to the first two decades of this century) that was represented by the observations that tumor cells were characterized by large hyperchromatic nuclei with excess of DNA and by abnormal mitoses (4,5). Genetic alterations appear to be linked to chromosomal aberrations and aneuploidy in cancer cells (6–11), but a cause-effect relationship is still unproven. The large number of genetic and chromosome changes detected by molecular biology, classical cytogenetics and, more recently, by chromosome painting and interphase cytogenetics using fluorescence in situ hybridization (12,13), appears simply too difficult to be set in a cause-effect relationship. An initial preneoplastic genetic event predisposing to more generalized disruption of the genome has been postulated (1). Fragility and instability of the chromosomes may imply a variety of inherited and acquired genetic mechanisms as well as the influence of environmental agents (14–16). Probably, specific genetic changes direct the process of aneuploidization. However, this is not the common view since many scientists believe that aneuploidy is an epiphenomenon of random origin.

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References

  1. J. Cairns. The origin of human cancer. Nature 289: 353 (1981).

    Article  PubMed  CAS  Google Scholar 

  2. R.A. Weinberg. Oncogenes, antioncogenes, and the molecular bases of multistep carcinogenesis. Cancer Res. 49: 3713 (1989).

    PubMed  CAS  Google Scholar 

  3. J.M. Bishop. The molecular genetics of cancer. Science 235: 305 (1987).

    Article  PubMed  CAS  Google Scholar 

  4. A.C. Broders. Carcinoma grading and practical application. Arch. Path. 2: 376 (1926).

    Google Scholar 

  5. T. Boveri. Zur Frage der Entstehung maligner Tumoren. Gustav Fisher Jcna (1914).

    Google Scholar 

  6. S. Heim and F. Mitelman. Chromosomal abnormalities in specific disorders: solid tumors. In: Heim S, Mitelman F, editors. Cancer cytogenetics. New York; Alan R. Liss Inc, p. 227 (1987).

    Google Scholar 

  7. P.C. Nowell. The clonal evolution of tumor cell populations. Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression. Science 194: 23 (1976).

    Article  PubMed  CAS  Google Scholar 

  8. L. Hartwell. Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. Cell 71: 543 (1992).

    Article  PubMed  CAS  Google Scholar 

  9. L. Hartwell and M.B. Kastan. Cell cycle control and cancer. Science 266: 1821 (1994).

    Article  PubMed  CAS  Google Scholar 

  10. W.K. Kaufmann. Cell cycle checkpoints and DNA repair preserve the stability of the human genome. Cancer Met. Rev. 14:31 (1995).

    Article  CAS  Google Scholar 

  11. T.D. Tlsty. Cell cycle control and genomic instability. Cancer Met. Rev. 14: 1 (1995).

    Article  Google Scholar 

  12. A.K. Raap, P.M. Nederlof, R.W. Dirks, J.C.A.G. Wiegant and M. van der Ploeg. Use of haptenize nucleic acid probes in fluorescent in situ hybridization. In: In situ hybridization: application to developmental biology and medicine. N. Harris and D?G? Williams (eds.). Great Britain, Cambridge University press p. 33 (1990).

    Chapter  Google Scholar 

  13. J.W. Gray and D. Pinkel. Molecular cytogenetics in human cancer diagnosis. Cancer 69: 1536 (1992).

    Article  PubMed  CAS  Google Scholar 

  14. J.J. Yunis and A.L. Soreng. Constitutive fragile sites and cancer. Science 226: 1199 (1984).

    Article  PubMed  CAS  Google Scholar 

  15. G.R. Sutherland and R.N. Simmers. No statistical association between common fragile sites and nonran-dom chromosomal breakpoints in cancer cells. Cancer Genet. Cytogenet. 31:9 (1988).

    Article  PubMed  CAS  Google Scholar 

  16. J.P.G. Volpe. Genetic instability of cancer: why a metastatic tumor is unstable and benign tumor is stable. Cancer Genet. Cytogenet. 34: 125 (1988).

    Article  PubMed  CAS  Google Scholar 

  17. B.E. Crawford and F.W. Stromeyer. Small nonpolypoid carcinoma of the large intestine. Cancer 51: 1760 (1983).

    Article  PubMed  CAS  Google Scholar 

  18. P. Correa, J.P. Strong, A. Reif and W.D. Johnson. The epidemiology of colorectal polyps. Prevalence in New Orleans and international comparison. Cancer 39: 2258 (1977).

    CAS  Google Scholar 

  19. B.C. Morson. The polyp-cancer sequence in the large bowel. Proc. Roy. Soc. Med. 67: 451 (1974).

    PubMed  CAS  Google Scholar 

  20. M. Risio, S. Coverlizza, A. Ferrari, G.L. Candelaresi and F.P. Rossini. Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas and adenocarcinomas of the large bowel. Gastroenterology 94: 899 (1988).

    PubMed  CAS  Google Scholar 

  21. E.R. Fearon and B. Vogelstein. A genetic model for colorectal tumorigenesis. Cell 61: 759 (1990).

    Article  PubMed  CAS  Google Scholar 

  22. W. Giaretti, S. Sciallero, S. Bruno, E. Geido, H. Aste and A. Di Vinci. DNA flow cytometry of endoscopi-cally examined colorectal adenomas and adenocarcinomas. Cytometry 9: 238 (1988).

    Article  PubMed  CAS  Google Scholar 

  23. M.J. O’Brien, S.J. Winawer, A.G. Zauber, B. Diaz, L.S. Gottlieb, J. Bond et al. The national polyp study: determinants of high grade dysplasia in colorectal adenomas. Gastroenterology 98: 371 (1990).

    PubMed  Google Scholar 

  24. G. Hoff, A. Foerster, M.J. Vatn, J. Savar and S. Larsen. Epidemiology of polyps in the rectum and colon. Recovery and evolution of unresected polyps 2 years after detection. Scand. J. Gastroenterol. 21: 853 (1986).

    Article  PubMed  CAS  Google Scholar 

  25. T.J. Eide. Risk of colorectal cancer in adenoma bearing individuals within a defined population. Int. J. Cancer 38: 173 (1986).

    Article  PubMed  CAS  Google Scholar 

  26. J.V. Selby, G.D. Friedman, C.P. Jr. Quesenberry and S.N. Weiss. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. New Engl. J. Med. 326: 659 (1992).

    Article  Google Scholar 

  27. B.C. Morson, I.M.P. Dawson, J.R. Jass, A.B. Price and G.T. Williams. Morson & Dawson’s gastrointestinal pathology. Third Edition. Blackwell Scientific Publications. Oxford, p. 577 (1990).

    Google Scholar 

  28. T. Muto, H.J.R. Bussey and B.C. Morson. The evolution of cancer of the colon and rectum. Cancer 36: 2251 (1975).

    Article  PubMed  CAS  Google Scholar 

  29. Y.S. Kim and S.H. Itskowitz. Carbohydrate antigen expression in the adenoma-carcinoma sequence. In: Basic and clinic perspectives of colorectal polyps and cancer. G. Jr. Steele, R. Burt, S.J. Winawer and J.P. Karr (eds.) New York, Alan R. Liss Inc., p. 241 (1988).

    Google Scholar 

  30. C.A. Rubio. Atypical mitosis in colorectal adenomas. Path. Res. Pract. 187: 508 (1991).

    Article  PubMed  CAS  Google Scholar 

  31. L.A. Cannon-Albright, M.H. Skolnick, D.T. Bishop, R.G. Lee and R.W. Burt. Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. New Engl. J. Med. 319: 533 (1988).

    Article  PubMed  CAS  Google Scholar 

  32. E. Solomon, R. Voss, V. Hall, W.F. Bodmer, J.R. Jass, A.J. Jeffreys, et al. Chromosome 5 allele loss in human colorectal carcinomas. Nature 328: 616 (1987).

    Article  PubMed  CAS  Google Scholar 

  33. G.C. Burmer and L.A. Loeb. Mutations in the K-ras2 oncogene during progressive stages of human colon carcinoma. Proc. Natl. Acad. Sci. 86: 2403 (1989).

    Article  PubMed  CAS  Google Scholar 

  34. B. Vogelstein, E.R. Fearon, S.R. Hamilton, S.E. Kern, A.C. Preisinger, B.A.M. Leppert, et al. Genetic alterations during colorectal-tumor development. New Engl. J. Med. 319: 525 (1988).

    Article  PubMed  CAS  Google Scholar 

  35. B. Vogelstein, E.R. Fearon, S.E. Kern, R.H. Stanley, A.C. Preisinger, Y. Nakamura, et al. Allelotype of colorectal carcinomas. Science 244: 207 (1989).

    Article  PubMed  CAS  Google Scholar 

  36. G.L. Nicolson. Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogenes to oncofetal expression. Cancer Res. 47: 1473 (1987).

    PubMed  CAS  Google Scholar 

  37. D.J. Slamon. Proto-oncogenes and human cancers. New Engl. J. Med. 317: 955 (1987).

    Article  PubMed  CAS  Google Scholar 

  38. S.H. Friend, T.P. Dryja and R.A. Weinberg. Oncogenes and tumor-suppressing genes. New Engl. J. Med. 318:618 (1988).

    Article  PubMed  CAS  Google Scholar 

  39. R. Muschel and L.A. Liotta. Role of oncogenes in metastases. Carcinogenesis 9: 705 (1988).

    Article  PubMed  CAS  Google Scholar 

  40. W. Giaretti, M. Danova, E. Geido, G. Mazzini, S. Sciallero, H. Aste et al. Flow cytometric DNA index in prognosis of colorectal cancer. Cancer 67: 1921 (1991).

    Article  PubMed  CAS  Google Scholar 

  41. W. Giaretti, N. Pujic, A. Rapallo, S. Nigro, A. Di Vinci, E. Geido and M. Risio. K-ras2 G-C and G-T trans-versions correlate with DNA aneuploidy in colorectal adenomas. Gastroenterology 108: 1040 (1995).

    Article  PubMed  CAS  Google Scholar 

  42. W. Giaretti and L. Santi. Tumor progression by DNA flow cytometry in human colorectal cancer. Int. J. Cancer 45: 597 (1990).

    Article  PubMed  CAS  Google Scholar 

  43. W. Giaretti. A model of DNA aneuploidization and evolution in colorectal cancer. Lab. Invest. 71: 904 (1994).

    PubMed  CAS  Google Scholar 

  44. H.F. Stich and H.D. Steele. Content of tumor cells. Quantitative genetic analysis of tumor progression. Cancer Met. Rev. 4: 173 (1962).

    Google Scholar 

  45. J.C. Fardon and J.E. Prince. A comparison of the ratios of metaphase to prophase in normal and neoplastic tissues. Cancer Res. 12: 793 (1952).

    PubMed  CAS  Google Scholar 

  46. T.C. Hsu and P.S. Moorhead. Chromosome anomalies in human neoplams with special reference to the mechanisms of polyploidization and aneuploidization in HeLa strain. Ann. NY Acad. Sci. 63: 1083 (1956).

    Article  PubMed  CAS  Google Scholar 

  47. S. Makino. Further evidence favoring the concept of the stem cell in ascites tumors of rats. Ann. NY Acad. Sci. 63: 818 (1956).

    Article  PubMed  CAS  Google Scholar 

  48. S. Makino. Neoplasia. In: Human Chromosomes. Igaku Shoin, Tokio, p. 429 (1987).

    Google Scholar 

  49. S.E. Shackney, C.A. Smith, B.W. Miller, D.R. Burholt, K. Murtha, H.R. Giles, et al. Model for the genetic evolution of human solid tumors. Cancer Res. 49: 3344 (1989).

    PubMed  CAS  Google Scholar 

  50. H.F. Van den Ingh, G. Griffioen and C.J. Comelisse. Flow cytometric detection of aneuploidy in colorectal adenomas. Cancer Res. 45: 3392 (1985).

    PubMed  Google Scholar 

  51. W.C. Dooley, D.C. Allison and J. Robertson. Discrepancies among the metaphase, telophase, and the G0/G1 and G2 DNA peaks of heteroploid cell lines. Cytometry 12: 99 (1991).

    Article  PubMed  CAS  Google Scholar 

  52. W.C. Dooley and D.C. Allison. Non-random distribution of abnormal mitoses in heteroploid cell lines. Cytometry 13: 462 (1992).

    Article  PubMed  CAS  Google Scholar 

  53. B. Dutrillaux, M. Gerbault-Seureau, Y. Remvikos, B. Zafrani and M. Prieur. Breast cancer genetic evolution: I. Data from cytogenetics and DNA content. Breast Cancer res. Treat. 19: 245 (1991).

    Article  PubMed  CAS  Google Scholar 

  54. T.J. Mitchison. Mitosis: basic concepts. Curr. Op. Cell Biol. 1: 67 (1989).

    Article  PubMed  CAS  Google Scholar 

  55. J.H. Ford. Chromosome dysplacement hypothesis. In: B.K. Vig and A.A. Sandberg (eds.). Aneuploidy, incidence and etiology. Alan R. Liss, New York (1987).

    Google Scholar 

  56. M. Muleris, R.J. Salmon and B. Dutrillaux. Cytogenetics of colorectal adenocarcinomas. Cancer Genet. Cytogenet. 46: 143 (1990).

    Article  PubMed  CAS  Google Scholar 

  57. A.C. Williams, S.J. Harper, C.J. Marshall, R.W. Gill, R.A. Mountford and C. Paraskeva. Specific cytogenetic abnormalities and K-ras mutation in two new human colorectal adenoma derived cell lines. Int. J. Cancer 52: 785 (1992).

    Article  PubMed  CAS  Google Scholar 

  58. G. Bardi, B. Johansson, N. Pandis, N. Mandahl, J.E. Bak, C. Lindstrom, et al. Cytogenetic analysis of 52 colorectal carcinomas: non-random aberration pattern and correlation with pathologic parameters. Int. J. Cancer 55: 422 (1993).

    Article  PubMed  CAS  Google Scholar 

  59. S. Nakamura, J. Goto, M. Kitayama and I. Kino. Application of the crypt-isolation technique to flow-cy-tometric analysis of DNA content in colorectal neoplasms. Gastroenterology 106: 100 (1994).

    PubMed  CAS  Google Scholar 

  60. G.J.A. Offerhaus, E.P. DeFeyter, C.J. Cornelisse, K.W.F. Tersmette, J. Floyd, S.E. Kern, et al. The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma. Gastroenterology 102: 1612 (1992).

    PubMed  CAS  Google Scholar 

  61. M. Kouri, A. Laasonen, J.P. Mecklin, H. Järvinen, K. Franssila and S. Pyrhönen. Diploid predominance in hereditary nonpolyposis colorectal carcinoma evaluated by flow cytometry. Cancer 65: 1825 (1990).

    Article  PubMed  CAS  Google Scholar 

  62. G.I. Meling, R.A. Lothe, A.L. Børresen, C. Graue, S. Hauge, O.P.F. Clausen, et al. The TP53 tumour suppressor gene in colorectal carcinomas. II. Relation to DNA ploidy pattern and clinicopathological variables. Br. J. Cancer 67: 93 (1993).

    Article  PubMed  CAS  Google Scholar 

  63. M.J. Mckinley, D.R. Budman, D. Grueneberg, R.L. Bronzo, G.S. Weissman and E. Kahn. DNA content in Barrett’s esophagus and esophageal malignancy. Am. J. Gastroenterol. 82: 1012 (1987).

    PubMed  CAS  Google Scholar 

  64. A. Zimmermann and F. Truss. The prognostic power of flow-through cytophotometric DNA determinations for testicular diseases. Anal. Quant. Cytol. 2: 247 (1980).

    PubMed  CAS  Google Scholar 

  65. E. Thorud, O.P.F. Clausen and T. Abyholm. Fine needle aspiration biopsies from human testes evaluated by DNA flow cytometry. In: O. Lareum, T. Lindmo and E. Thorud (eds.). Flow Cytometry vol. IV. Oslo, Universitetsforlaget, p. 175 (1981).

    Google Scholar 

  66. P. Pfitzer, P. Gilbert, G. Roly and K. Vyska. Flow cytometry of human testicular tissue. Cytometry 3: 116 (1982).

    Article  PubMed  CAS  Google Scholar 

  67. D.P. Evenson and M.R. Melamed. Rapid analysis of normal and abnormal cell types in human semen and testis biopsies by flow cytometry. J. Histochem. Cytochem. 31: 248 (1983).

    Article  PubMed  CAS  Google Scholar 

  68. B. Tribukait. DNA flow cytometry in carcinoma of the prostate for diagnosis, prognosis and study of tumor biology. Acta Oncologica 30: 187 (1991).

    Article  PubMed  CAS  Google Scholar 

  69. S. Pulciani, E. Santos, A.V. Lauver, L.K. Long, S.A. Aaronson and D. Barbacid. Oncogenes in solid human tumours. Nature 300: 539 (1982).

    Article  PubMed  CAS  Google Scholar 

  70. D.A. Spandidos and N.M. Wilkie. Malignant transformation of early-passage rodent cells by a single mutated human oncogene. Nature 310: 469 (1984).

    Article  PubMed  CAS  Google Scholar 

  71. J.E. de Vries, F.H.A.C. Kornips, P. Marx, F.T. Bosman, J.P.M. Geraedts and J. Kate. Transfected c-Ha-ras oncogene enhances karyotypic instability and integrates predominantly in aberrant chromosomes. Cancer Genet. Cytogenet. 65: 35 (1993).

    Article  Google Scholar 

  72. N. Hagag, L. Diamond, R. Palermo and S. Lyubsky. High expression of ras p21 correlates with increased rate of abnormal mitosis in NIH3T3 cells. Oncogene 5: 1481 (1990).

    PubMed  CAS  Google Scholar 

  73. J.L. Bos, E.R. Fearon, S.R. Hamilton, M. Verlaan de Vries, J.H. van Boom, A.J. van der Eb and B. Vogel-stein. Prevalence of ras gene mutations in human colorectal cancers. Nature 327: 293 (1987).

    Article  PubMed  CAS  Google Scholar 

  74. S. Nigro, E. Geido, E. Infusini, R. Orecchia and W. Giaretti. Transfection of human mutated K-ras in mouse NIH-3T3 cells is associated with increased cloning efficiency and DNA aneuploidization. Int. J. Cancer 67: 1 (1996).

    Article  Google Scholar 

  75. W. Giaretti, R. Monaco, N. Pujic, A. Rapallo, S. Nigro and E. Geido. Intratumor heterogeneity of K-ras2 mutations in colorectal adenocarcinomas. Association with degree of DNA aneuploidy. Am.J. Pathology 149:1 (1996).

    Google Scholar 

  76. D.P. Lane. p53, guardian of the genome. Nature 358:15 (1992).

    Google Scholar 

  77. M.S. Greenblatt, WP. Bennet, M. Hollstein, C.C. Harris. Mutations in the p53 suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54 (1994).

    Google Scholar 

  78. P.C. Galipeau, D.S. Cowan, C.A. Sanchez, M.T. Barrett, M.J. Emond, D.S. Levine, P.S. Rabinovitch and B.J. Reid. 17p (p53) allelic losses, 4N (G2/tetraploid) populations, and progression to aneuploidy in Barrett’s esophagus. Prc. Natl. Acad. Sci. USA 93 (1996).

    Google Scholar 

  79. A. Di Vinci, E. Infusini, C. Peveri, M. Risio, F.P. Rossini and W. Giaretti. Deletions at chromosome 1p by fluorescence in situ hybridization are an early event in human colorectal tumorigenesis. Gastroenterology 111: 102 (1996).

    Article  PubMed  Google Scholar 

  80. G. Bardi, N. Pandis, C. Fenger, O. Kronborg, L. Bomme and S. Heim. Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis. Cancer Res. 53: 1895 (1993).

    PubMed  CAS  Google Scholar 

  81. C.A. Griffin, S. Lazer, S.R. Hamilton, F.M. Giardiello, P. Long, A.J. Krush and S.V. Booker. Cytogenetic analysis of intestinal polyps in polyposis syndromes: Comparison with sporadic colorectal adenomas. Cancer Genet. Cytogenet. 67: 14 (1993).

    Article  PubMed  CAS  Google Scholar 

  82. M. Longy, R. Saura, F. Dumas, J.F. Leseve, L. Taine, J.F. Goussot and P. Couzigou. Chromosome analysis of adenomatous polyps of the colon. Cancer Genet. Cytogenet. 67: 7 (1993).

    Article  PubMed  CAS  Google Scholar 

  83. L. Bomme, G. Bardi, N. Pandis, C. Fenger, O. Kronborg and S. Heim. Clonal karyotypic abnormalities in colorectal adenomas: clues to the early genetic events in the adenoma-carcinoma sequence. Genes Chromosom. Cancer 10: 190 (1994).

    Article  PubMed  CAS  Google Scholar 

  84. J. Herbergs, A.P. de Bruine, P.T.J. Marx, M.I.J. Vallinga, R.W. Stockbrügger, F.C.S. Ramaekers, J.W. Arends and A.H.N. Hopman. Chromosome aberrations in adenomas of the colon. Proof of trisomy 7 in tumor cells by combined interphase cytogenetics and immunohistochemistry. Int. J. Cancer 57: 781 (1994).

    Article  PubMed  CAS  Google Scholar 

  85. B.A. Bunnell, L.S. Heath, D.E. Adams, J.M. Lahti and V.J. Kidd. Increased expression of a 58-kDa protein kinase leads to changes in the CHO cell cycle. Proc. Natl. Acad. Sci. USA 87: 7467 (1990).

    Article  PubMed  CAS  Google Scholar 

  86. J.M. Lahti, J. Xiang, L.S. Heath, D. Campana and V.J. Kidd. PITSLRE protein kinase activity is associated with apoptosis. Mol. Cell. Biol. 15: 1 (1995).

    PubMed  CAS  Google Scholar 

  87. P. Engler, P. Haasch, C.A. Pinkert, et al. A strain-specific modifier on mouse chromosome 4 controls the methylation of independent transgene loci. Cell 65: 939 (1991).

    Article  PubMed  CAS  Google Scholar 

  88. S.E. Goelz, B. Vogelstein, S.R. Hamilton and A.P. Feinberg. Hypomethylation of DNA from benign and malignant human colon neoplams. Science 228: 187 (1985).

    Article  PubMed  CAS  Google Scholar 

  89. A. Almeida, N. Kokalj-Vokac, D. Lefrancois, E. Viegas-Péquignot, M. Jeanpierre, B. Dutrillaux and B. Malfoy. Hypomethylation of classical satellite DNA and chromosome instability in lymphoblastoid cell lines. Hum. Genet. 91:538 (1993).

    Article  PubMed  CAS  Google Scholar 

  90. H.M. Foss, C.J. Roberts, K.M. Claeys and E.U. Selker. Abnormal chromosome behavior in neurospora mutants defective in DNA methylation. Science 262: 1737 (1993).

    Article  PubMed  CAS  Google Scholar 

  91. H. Stopper, C. Körber, D. Schiffmann and W.J. Caspary. Cell-cycle dependent micronucleus formation and mitotic disturbances induced by 5-azacytidine in mammalian cells. Mut. Res. 300: 165 (1993).

    Article  CAS  Google Scholar 

  92. G. Poste, J. Doll and I.J. Fidler. Interactions between clonal subpopulations affect the stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells. Proc. Natl. Acad. Sci. 78: 6226 (1981).

    Article  PubMed  CAS  Google Scholar 

  93. A. Hall. Small GTP-binding proteins and the regulation of the actin cytoskeleton. Annu. Rev. Cell Biol. 10: 31 (1994).

    Article  PubMed  CAS  Google Scholar 

  94. C.D. Nobes and A. Hall. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81: 53 (1995).

    Article  PubMed  CAS  Google Scholar 

  95. D.A. Larochelle, K.K. Vithalani and A. De Lozanne. A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis. J. Cell Biol. 133: 1321 (1996).

    Article  PubMed  CAS  Google Scholar 

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  1. Laboratory of Biophysics and Cytometry, National Institute for Cancer Research, Genoa, Italy

    Walter Giaretti

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  1. Roswell Park Cancer Institute, Buffalo, New York, USA

    Enrico Mihich

  2. University of Washington, Seattle, Washington, USA

    Leland Hartwell

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Giaretti, W. (1997). Aneuploidy and Heterogeneity Mechanisms in Human Colorectal Tumor Progression. In: Mihich, E., Hartwell, L. (eds) Genomic Instability and Immortality in Cancer. Pezcoller Foundation Symposia, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5365-6_4

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