Genomic Instability in Cancer I: DNA-Repair Triggering Primitive Hereditary 4n-Skewed, Amitotic Division-System, the Culprit in EMT/MET/Metaplasia Cancer-Concepts — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Genomic Instability in Cancer I: DNA-Repair Triggering Primitive Hereditary 4n-Skewed, Amitotic Division-System, the Culprit in EMT/MET/Metaplasia Cancer-Concepts
The objective was to gain proof of genome damage-repair induced mitotic slippage process (MSP) to 4n-diplochromosome skewed division-system, earlier suggested to have “cancer-deciding” consequences. Our damage-model showed two succeeding phases : molecular mutations for initiation of fitness-gained cells, and large chromosomal changes to aneuploidy from inherited DNA-breakage-repair inaccuracies. The mutations were gained while DNA-repair and DNA-replication, co-existed in the route to tetraploidy, a phenomenon also expressed for some existing unicellular organisms. These organisms also showed genome reductive, amitotic, meioticlike division, and was the origin of human genome conserved, self-inflicted 90 ° reorientation of the 4n nucleus relative to the cytoskeleton axis. In the in vitro DNA-damage model , this remarkable 4n-event deciding “flat-upright” cell-growth characteristics showed several consequences, for example, cancer-important, E-cad herin- β -catenin cell-to-cell adherence destruction, which gave diploid progeny cells, mobility freedom from cell contact inhibition, likely in renewal tissues. This 4n-skewed division-system with inheritance in progeny cells for repeat occurrences as mentioned for flat-up-right growth patterns is similar to claimed concepts of metaplasia-EMT/MET embryogenesis events in cancer evolution. A scrutiny of this literature, proof-wise invalidated this embryological concept by tetraploid 8C cells occurring in MET events and, was noted for small cell occurrence, i.e. , diploidy from 4n-8C reductive division, an also event for tumor relapse cells, derived from genome damaging therapy agents. Pre-cancer hyperplasia reported MSP, cadherincatenin destruction and 90 ° perpendicularity to basal cell membrane. The DNA-damage-repair model can weed-out therapy-agents triggering 4n-skewed division. Cancer-control, beginning-information, is likely from mutational identity of the 4n derived fitness-gained cells.
Ledford, H. (2010) The Cancer Genome Challenge. Nature, 464, 972-974. https://doi.org/10.1038/464972a
Lengauer, C., Kinzler, K.W. and Vogelstein, B. (1998) Genetic Instability in Human Cancers. Nature, 396, 643-649. https://doi.org/10.1038/25292
Nik-Zanail, S., Davies, H., Staff, J., Ramakrishna, M., Glodzik, D., Xou, X., Martincorena, I., et al. (2016) Landscape of Somatic Mutations in 560 Breast Cancer Whole Genome Sequences. Nature, 534, 47-54. https://doi.org/10.1038/nature17676
Nowak, M.A. and Waclaw, B. (2017) Genes, Environment, and “Bad Luck”. Science, 355, 1266-1267. https://doi.org/10.1126/science.aam9746
Tomasetti, C., Vogelstein, B. and Parmigiani, G. (2013) Half or More of the Somatic Mutations in Cancers of Self-Renewing Tissues Originate Prior to Tumor Initiation. Proceedings of the National Academy of Sciences of the USA, 110, 1999-2004. https://doi.org/10.1073/pnas.1221068110
Tomasetti, C., Marchionni, L., Nowak, M.A., Parmigiani, G. and Vogelstein, B. (2015) Only Three Driver Gene Mutations Are Required for the Development of Lung and Colorectal Cancers. Proceedings of the National Academy of Sciences of the USA, 112, 118-123. https://doi.org/10.1073/pnas.1421839112
Tomasetti, C., Li, L. and Vogelstein, B. (2017) Stem Cell Divisions, Somatic Mutations, Cancer Etiology, and Cancer Prevention. Science, 355, 1330-1334. https://doi.org/10.1126/science.aaf9011
Weinberg, R.A. (2014) Coming Full Circle—From Endless Complexity to Simplicity and Back Again. Cell, 157, 267-271. https://doi.org/10.1016/j.cell.2014.03.004
Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674. https://doi.org/10.1016/j.cell.2011.02.013
Li, R., Sonik, A., Stindl, R., Rasnick, D. and Duesberg, P. (2000) Aneuploidy vs. Gene Mutation Hypothesis of Cancer: Recent Study Claims Mutation but Is Found to Support Aneuploidy. Proceedings of the National Academy of Sciences of the USA, 97, 3236-3241. https://doi.org/10.1073/pnas.97.7.3236
Walen, K.W. and Stampfer, M.R. (1989) Chromosome Analyses of Human Mammary Epithelial Cells at Stages of Chemical-Induced Transformation Progression to Immortality. Cancer Genetics and Cytogenetics, 37, 249-261. https://doi.org/10.1016/0165-4608(89)90056-3
Bozic, I., Antal, T., Ohtsuki, H., Carter, H., Kim, D., Chen, S., Karchin, R., et al. (2010) Accumulation of Driver and Passenger Mutations during Tumor Progression. Proceedings of the National Academy of Sciences of the USA, 107, 18545-18550. https://doi.org/10.1073/pnas.1010978107
Embryogenesis-Type EMT/MET
Human Cell Conservation
Cairns, J. (1983) Cancer: Science and Society. W.H. Freeman & Company.
Kinzler, K.W., Nowak, M.A., Komarova, N.L., Sengupta, A., Jallepalli, P.V., Shih, le-M. and Vogelstein, B. (2002) The Role of Chromosomal Instability in Tumor Initiation. Proceedings of the National Academy of Sciences of the USA, 99, 16226-16231. https://doi.org/10.1073/pnas.202617399
Rubin, H. (1993) Epigenetic Nature of Neoplastic Transformation. In: Hodges, G.M. and Rowlett, Eds., Developmental Biology and Cancer, CRC Press, Ann Arbor.
Holland, A.J. and Cleveland, D.W. (2012) Losing Balance: The Origin and Impact of Aneuploidy in Cancer. EMBO Reports, 13, 501-514. https://doi.org/10.1038/embor.2012.55
Sanghee, L. and Ganem, N.J. (2014) Tetraploidy and Tumor Development. Oncotarget, 5, 10959-10960.
Sheltzer, J.M. and Amon, A. (2011) The Aneuploidy Paradox: Costs and Benefits of an Incorrect Karyotype. Trends in Genetics, 27, 446-453. https://doi.org/10.1016/j.tig.2011.07.003
Walen, K.H. (2012) Genome Reversion Process of Endopolyploidy Confers Chromosome Instability on the Descendent Diploid Cells. Cell Biology International, 36, 137-145. https://doi.org/10.1042/CBI20110052
Walen, K.H. (2016) Cancer Prevention: Fundamental Genomic Alterations Are Present in Preneoplasia Including Function of High Frequency Selected Mutations (HFSM). Journal of Cancer Therapy, 7, 416-426. https://doi.org/10.4236/jct.2016.76044
Walen, K. (2017) Mitotic Slippage Process Concealed Cancer-Sought Chromosome Instability Mechanism (S-CIN). Journal of Cancer Therapy, 8, 608-623. https://doi.org/10.4236/jct.2017.86052
Weaver, B.A.A. and Cleveland, D.W. (2009) The Role of Aneuploidy in Promoting and Suppressing Tumors. The Journal of Cell Biology, 185, 935-937. https://doi.org/10.1083/jcb.200905098
Wood, L.D., Parsons, D.W., Jones, S., Lin, J., Sjoblom, T., Leary, R.J., et al. (2007) The Genomic Landscapes of Human Breast and Colorectal Cancer. Science, 318, 1108-1113. https://doi.org/10.1126/science.1145720
Kelty, P.N. (2018) The Cancer Immunotherapy Revolution. Science, 359, 1345-1370.
Mueller, K.L. (2015) Realizing the Promise. Science, 348, 54-55.
Pattabiraman, D.R., Bierie, B., Kober, K.I., Thiru, P., Krall, J.A., Zill, C., Reinhardt, F., Tam, W.L. and Weinberg, R.A. (2016) Activation of PKA Leads to Mesenchymal-to-Epithelial Transition and Loss of Tumor-Initiating Ability. Science, 351, aad3680. https://doi.org/10.1126/science.aad3680
Stratton, M.R., Campbell, P.J. and Futreal, P.A. (2009) The Cancer Genome. Nature, 458, 719-724. https://doi.org/10.1038/nature07943
Loeb, L.A., Bielas, J.H., Beckman, R.A. and Bodmer, I.W. (2008) Cancers Exhibit a Mutator Phenotype: Clinical Implications. Cancer Research, 68, 3551-3557. https://doi.org/10.1158/0008-5472.CAN-07-5835
Bodmere, W. and Loeb, L.A. (2008) Genetic Instability Is Not a Requirement for Tumor Development. Cancer Research, 68, 3558-3561. https://doi.org/10.1158/0008-5472.CAN-07-6544
Vincent, M.D. (2010) The Animal Within: Carcinogenesis and Clonal Evolution of Cancer Cells Are Speciation Events Sensu Stricto. Evolution, 64, 1173-1183. https://doi.org/10.1111/j.1558-5646.2009.00942.x
Kaiser, J. (2012) Cancer Genetics with an Edge. Science, 337, 282-284. https://doi.org/10.1126/science.337.6092.282
Liu, J.K. (2014) Anti-Cancer Vaccines—A One Hit Wonder? Yale Journal of Biology and Medicine, 87, 481-489.
Mitelman, F. (1988) Catalog of Chromosome Aberrations in Cancer. Alan Liss, Inc., New York.
Heim, S. and Mitelman, F. (1995) Cancer Cytogenetics: Chromosomal and Molecular Genetic Aberrations of Tumor Cells. 2nd Edition, Wiley-Liss, Inc., New York.
Mandahl, N., Johansson, B., Mertens, F. and Mitelman, F. (2012) Disease-Associated Patterns of Disomic Chromosomes in Hyperhaploid Neoplasms. Genes, Chromosomes and Cancer, 51, 536-544. https://doi.org/10.1002/gcc.21947
Bayani, J., Paderova, J., Murphy, J., Rosen, B., Zielenska, M. and Squire, J.A. (2008) Distinct Patterns of Structural and Numerical Chromosomal Instability Characterize Sporadic Ovarian Cancer. Neoplasia, 10, 1057-1065. https://doi.org/10.1593/neo.08584
Fearon, E.R. and Vogelstein, B. (1990) A Genetic Model of Colorectal Tumorigenesis. Cell, 61, 759-767. https://doi.org/10.1016/0092-8674(90)90186-I
Margolis, R.L. (2005) Tetraploidy and Tumor Development. Cancer Cell, 8, 353-354. https://doi.org/10.1016/j.ccr.2005.10.017
Walen, K.H. (2006) Human Diploid Fibroblast Cells in Senescence: Cycling from Polyploidy to Mitotic Cells. In Vitro Cellular & Developmental Biology-Animal, 42, 216-224. https://doi.org/10.1290/0603019.1
Benn, P.A. (1976) Specific Chromosome Aberrations in Senescent Fibroblast Cell Lines Derived from Human Embryos. American Journal of Human Genetics, 28, 465-473.
Davoli, T., Denchi, E.L. and de Lange, T. (2010) Persistent Telomere Damage Induces Bypass of Mitosis and Tetraploidy. Cell, 141, 81-93. https://doi.org/10.1016/j.cell.2010.01.031
Brito, D. and Rieder, C.L. (2006) Mitotic Slippage in Humans Occurs via Cyclin B Destruction in the Presence of an Active Checkpoint. Current Biology, 16, 1194-1200. https://doi.org/10.1016/j.cub.2006.04.043
Cantor, J.R. and Sabatini, D.M. (2012) Cancer Cell Metabolism: One Hallmark, Many Faces. Cancer Discovery, 2, 881-898. https://doi.org/10.1158/2159-8290.CD-12-0345
Walen, K.H. (2007) Bipolar Genome Reductional Division of Human Near-Senescent, Polyploid Fibroblast Cells. Cancer Genetics and Cytogenetics, 173, 43-50. https://doi.org/10.1016/j.cancergencyto.2006.09.013
Walen, K.H. (2007) Origin of Diplochromosomal Polyploidy in Near-Senescent Fibroblast Cultures: Telomeres and Chromosomal Stability (CIN). Cell Biology International, 31, 1447-1455. https://doi.org/10.1016/j.cellbi.2007.06.015
Swanson, C.P. (1957) Cytology and Cytogenetics. Prentice-Hall, Englewood Cliffs, NJ.
Zybina, E.V., Zybina, T.G., Bogdanova, M.S. and Stein, G.I. (2005) Whole-Genome Chromosome Distribution during Nuclear Fragmentation of Giant Cells of Microtus rossiaemeridionalis Studies by Use of Gonosomal Chromatin Arrangement. Cell Biology International, 29, 1066-1070. https://doi.org/10.1016/j.cellbi.2005.10.014
Brenner, S., Branch, A., Meredith, S. and Berns, M.W. (1977) The Absence of Centrioles from Spindle Poles of Rat Kangaroo (PtK2) Cells Undergoing Meiotic-Like Reduction Division in Vitro. The Journal of Cell Biology, 72, 368-379. https://doi.org/10.1083/jcb.72.2.368
Vitale, I. and Kroemer, G. (2017) Spontaneous DNA Damage Propels Tumorigenicity. Cell Research, 27, 720-721. https://doi.org/10.1038/cr.2017.43
Argueso, J.L., Westmoreland, J., Mieczkowski, P.A., Gawel, M., Petes, T.D. and Resnick, M.A. (2008) Double-Strand Breaks Associated with Repetitive DNA Can Reshape the Genome. Proceedings of the National Academy of Sciences of the United States of America, 105, 11845-118450. https://doi.org/10.1073/pnas.0804529105
Stephens, P.J., Greenman, C.D., Fu, B., Yang, F., Bignell, G.R., Mudie, L.J., Pleasance, E.D., Lau, K.W., et al. (2011) Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development. Cell, 144, 27-40. https://doi.org/10.1016/j.cell.2010.11.055
Przybytkowski, E., Lenkiewicz, E., Barrett, M.T., Klein, K., Nabavi, S., Greenwood, C.M.T. and Basik, M. (2014) Chromosome-Breakage Genomic Instability and Chromothripsis in Breast Cancer. BMC Genomics, 15, 579-592. https://doi.org/10.1186/1471-2164-15-579
Durkin, S.G. and Glover, T.W. (2007) Chromosome Fragile Sites. Annual Review of Genetics, 41, 169-192. https://doi.org/10.1146/annurev.genet.41.042007.165900
Walen, K.H. (2002) The Origin of Transformed Cells: Studies of Spontaneous and Induced Cell Transformation in Cell Cultures from Marsupials, a Snail and Human Amniocytes. Cancer Genetics and Cytogenetics, 133, 45-54. https://doi.org/10.1016/S0165-4608(01)00572-6
Walen, K.H. (1965) Spatial Relationships in the Replication of Chromosomal DNA. Genetics, 51, 915-929.
Deem, A., Keszthelyl, A., Blackgrove, T., Vayl, A., Coffey, B., Mathur, R. and Chabes, A. (2011) Break-Induced Replication Is Highly Inaccurate. PLoS Biology, 9, e1000594. https://doi.org/10.1371/journal.pbio.1000594
Unal, E., Heidinger-Pauli, J.M. and Koshland, D. (2007) DNA Double Strand Breaks Trigger Genome-Wide Sister-Chromatid Cohesion through Eco1 (Ctf7). Science, 317, 245-248. https://doi.org/10.1126/science.1140637
Uhlmann, F. (2009) A Matter of Choice: The Establishment of Sister Chromatid Cohesion. EMBO Reports, 10, 1095-1102. https://doi.org/10.1038/embor.2009.207
Harris, H. (1995) The Cells of the Body: A History of Somatic Cell Genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.
Sonnenschein, C. and Soto, A.M. (1999) The Society of Cells. BIOS Scientific Publishers Ltd., Oxford, UK.
Sonnenschein, C. and Soto, A.M. (2013) The Aging of the 2000 and 2011 Hallmarks of Cancer Reviews: A Critique. Journal of Biosciences, 38, 651-663. https://doi.org/10.1007/s12038-013-9335-6
Gumbiner, B.M. and Kim, N.-G. (2014) The Hippo-YAP Signaling Pathway and Contact Inhibition of Growth. Journal of Cell Science, 127, 709-717. https://doi.org/10.1242/jcs.140103
Soto, A.M., Maffini, M.V. and Sonnenschein, C. (2008) Neoplasia as Development Gone Awry: The Role of Endocrine Disruptors. International Journal of Andrology, 31, 288-293. https://doi.org/10.1111/j.1365-2605.2007.00834.x
Bignold, L.P., Coghlan, B.L.D. and Jersmann, H.P.A. (2007) David von Hansemann: Contributions to Oncology, Context, Comments, and Translations. Birkhauser Verlag, Basel, Switzerland.
Kalluri, R. and Weinberg, R.A. (2009) The Basics of Epithelial-Mesenchymal Transition. Journal of Clinical Investigation, 119, 1420-1428. https://doi.org/10.1172/JCI39104
Hirohashi, S. (1998) Inactivation of the E-Cadherin-Mediated Cell Adhesion System in Human Cancers. The American Journal of Pathology, 153, 333-339. https://doi.org/10.1016/S0002-9440(10)65575-7
Saito, A., et al. (1999) Disruption of E-Cadherin-Mediated Cell Adhesion System in Gastric Cancers of Young Patients. Japanese Journal of Cancer Research, 90, 993-999. https://doi.org/10.1111/j.1349-7006.1999.tb00847.x
Morales, C.P., Souza, R.F. and Spechler, S.J. (2002) Hallmarks of Cancer Progression in Barrett’s Oesophagus. The Lancet, 360, 1587-1589. https://doi.org/10.1016/S0140-6736(02)11569-8
Dikovskaya, D., Schiffmann, D., Newton, I.P., Oakley, A., Kroboth, K., Sansom, O., et al. (2007) Loss of APC Induces Polyploidy as a Result of a Combination of Defects in Mitosis and Apoptosis. The Journal of Cell Biology, 176, 183-193. https://doi.org/10.1083/jcb.200610099
Coldwell, C.M., Green, R.A. and Kapland, K.B. (2007) APC Mutation Lead to Cytokinetic Failures in Vitro and Tetraploid Genotypes in Min Mice. The Journal of Cell Biology, 178, 1109-1120. https://doi.org/10.1083/jcb.200703186
Kim, N.-G., Koh, E., Chen, X. and Gumbiner, B.M. (2011) E-Cadherin Mediates Contact Inhibition of Proliferation through Hippo Signaling Pathway Components. Proceedings of the National Academy of Sciences of the United States, 108, 11930-11935. https://doi.org/10.1073/pnas.1103345108
Thiery, J.P. and Huang, R. (2005) Linking Epithelial-Mesenchymal Transition to the Well-Known Polarity Protein Par6. Developmental Cell, 8, 456-458. https://doi.org/10.1016/j.devcel.2005.03.002
Streichan, S.J., Hoerner, C.R., Schneidt, T., Holzer, D. and Hufnagel, L. (2014) Spatial Constraints Control Cell Proliferation in Tissues. Proceedings of the National Academy of Sciences of the United States, 111, 5586-5591. https://doi.org/10.1073/pnas.1323016111
Walen, K.H. (2011) Normal Human Cell Conversion to 3-D Cancer-Like Growth: Genome Damage, Endopolyploidy, Senescence Escape, and Cell Polarity Change/ Loss. Journal of Cancer Therapy, 2, 181-189. https://doi.org/10.4236/jct.2011.22023
Walen, K.H. (2013) Senescence Arrest of Endopolyploid Cells Renders Senescence into One Mechanism for Positive Tumorigenesis. In: Hayat, M., ed., Tumor Dormancy, Quiescence, and Senescence, Vol. 1, Springer, Dordrecht, 215-226. https://doi.org/10.1007/978-94-007-5958-9_18
Ronnov-Jensen, L., Petersen, O.W. and Bissell, M.J. (1996) Cellular Changes Involved in Conversion of Normal to Malignant Breast: Importance of the Stromal Reaction. Physical Review, 76, 69-125.
Saunders, W.S., Shuster, M., Huang, X., Gharaibe, B., Enyenihi, A.H., Petersen, J. and Gollin, S.M. (2000) Chromosomal Instability and Cytoskeleton Defects in Oral Cancer. Proceedings of the National Academy of Sciences of the United States, 97, 303-308. https://doi.org/10.1073/pnas.97.1.303
Royer, C. and Lu, X. (2011) Epithelial Cell Polarity: A Major Gatekeeper against Cancer? Cell Death & Differentiation, 18, 1470-1477. https://doi.org/10.1038/cdd.2011.60
Wodarz, A. and Nathke, I. (2007) Cell Polarity in Development and Cancer. Nature Cell Biology, 9, 1016-1024. https://doi.org/10.1038/ncb433
Barrett, M.T., Pritchard, D., Palanca-Wessels, C., Anderson, J., Reid, B.J. and Rabinovitch, P.S. (2003) Molecular Phenotype of Spontaneously Arising 4N (G2-Tetraploid) Intermediates of Neoplastic Progression in Barrett’s Esophagus. Cancer Research, 63, 4211-4217.
Steinbeck, R.G. (2004) Dysplasia in View of the Cell Cycle. European Journal of Histochemistry, 48, 203-211.
Davoli, T. and de Lange, T. (2012) Telomere-Driven Tetraploidization Occurs in Human Cells Undergoing Crisis and Promotes Transformation of Mouse Cells. Cancer Cell, 21, 765-776. https://doi.org/10.1016/j.ccr.2012.03.044
Ceol, C.J., Pellman, D. and Zon, L.I. (2007) APC and Colon Cancer: Two Hits for One. Nature Medicine, 13, 1286-1287. https://doi.org/10.1038/nm1107-1286
Aoki, K. and Taketo, M.M. (2007) Adenomatous Polyposis Coli (APC): A Multi-Functional Tumor Suppressor Gene. Journal of Cell Science, 120, 3327-3335. https://doi.org/10.1242/jcs.03485
Chan, K.L., Palmai-Pallag, T., Ying, S. and Hickson, I.D. (2009) Replication Stress Induces Sister-Chromatid Bridging at Fragile Site Loci in Mitosis. Nature Cell Biology, 11, 753-760. https://doi.org/10.1038/ncb1882
Gisselsson, D., Petterson, L., Hoglund, M., Heldenbla, M., Gorunova, L., Wiegant, J., Mertens, F., DalCin, P., Mitelman, F. and Mandahl, N. (2000) Chromosomal Breakage-Fusion-Bridge Events Cause Genetic Intratumor Heterogeneity. Proceedings of the National Academy of Sciences of the United States, 97, 5357-5362. https://doi.org/10.1073/pnas.090013497
Blagosklonny, M.V. (2007) Cancer Stem Cell and Cancer Stemloids. Cancer Biology & Therapy, 6, 1684-1690. https://doi.org/10.4161/cbt.6.11.5167
Kendall, S.D., Linardi, C.M., Adam, S.J. and Counter, C.M. (2005) A Network of Genetic Events Sufficient to Convert Normal Human Cells to a Tumorigenic State. Cancer Research, 65, 9824-9828. https://doi.org/10.1158/0008-5472.CAN-05-1543
Hahn, W.C., Counter, C.M., Lundberg, A.S., Beijersbergen, R.L., Brooks, M.W. and Weinberg, R.A. (1999) Creation of Human Tumor Cells with Defined Genetic Elements. Nature, 400, 464-468. https://doi.org/10.1038/22780
Garbe, J.C., Vrba, L., Sputova, K., Fuchs, L., Novak, P., Brothman, A.R., Jackson, M., et al. (2014) Immortalization of Normal Human Mammary Epithelial Cell in Two Steps by Direct Targeting of Senescence Barriers Does Not Require Gross Genomic Alterations. Cell Cycle, 13, 3423-3435. https://doi.org/10.4161/15384101.2014.954456
Lee, J.K., Garbe, J.C., Vrba, L., Mivano, M., Futscher, B.W., Stampfer, M.R. and LaBarge, M.A. (2015) Age and the Means of Bypassing Stasis Influence the Intrinsic Subtype of Immortalized Human Epithelial Cells. Frontiers in Cell and Developmental Biology, 3, 13. https://doi.org/10.3389/fcell.2015.00013
Solari, A.J. (2002) Primitive Forms of Meiosis: The Possible Evolution of Meiosis. Biocell, 26, 1-13.
Castagnetti, S., Oliferenko, S. and Nurse, P. (2010) Fission Yeast Cells Undergo Nuclear Division in the Absence of Spindle Microtubules. PLoS Biology, 8, e1000512. https://doi.org/10.1371/journal.pbio.1000512
Walen, K.H. (2009) Spindle Apparatus Uncoupling in Endo-Tetraploid Asymmetric Division of Stem and Non-Stem Cells. Cell Cycle, 8, 3234-3237. https://doi.org/10.4161/cc.8.19.9570
Raikov, I.B. (1994) The Diversity of Forms of Mitosis in Protozoa: A Comparative Review. European Journal of Protistology, 30, 253-269. https://doi.org/10.1016/S0932-4739(11)80072-6
Grell, K.G. and Ruthmann, A. (1964) Uber die Karyologie des Radiolars Aulacantha scolymantha und Feinstruktur seiner Chromosomen. Chromosoma, 15, 185-211. https://doi.org/10.1007/BF00285729
Niculescu, V. (2018) Carcinogenesis: Recent Insight in Protist Stem Cell Biology Lead to a Better Understanding of Atavistic Mechanisms Implied in Cancer Development. MOJ Tumor Research, 1, 18-29.
Haig, D. (1993) Alternatives to Meiosis: The Unusual Genetics of Red Algae, Microsporidia, and Others. Journal of Theoretical Biology, 163, 15-31. https://doi.org/10.1006/jtbi.1993.1104
Hurst, L.D. and Nurse, P. (1991) A Note on the Evolution of Meiosis. Journal of Theoretical Biology, 150, 561-565. https://doi.org/10.1016/S0022-5193(05)80447-3
Kondrashov, A.S. (1994) The Asexual Ploidy Cycle and the Origin of Sex. Nature, 370, 213-216. https://doi.org/10.1038/370213a0
Fernholm, A. (2015) DNA Repair—Providing Chemical Stability for Life. The Royal Swedish Academy of Sciences.
Lucchetta, E.M. and Ohlstein, B. (2017) Amitosis of Polyploid Cells Regenerates Functional Stem Cells in Drosophila Intestine. Cell Stem Cell, 20, 609-620. https://doi.org/10.1016/j.stem.2017.02.012
Agrawal, N., Jiao, Y., Bettegowda, C., Hutfless, S.M., Wang, Y., David, S., et al. (2012) Comparative Genomic Analysis of Esophageal Adenocarcinoma and Squamous Cell Carcinoma. Cancer Discovery, 2, 899-905. https://doi.org/10.1158/2159-8290.CD-12-0189
Stachler, M.D., Tailor-Weiner, A., Peng, S., McKenna, A., Agoston, A.T., Odze, R.D., Davison, J.M., et al. (2015) Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma. Nature Genetics, 47, 1047-1055. https://doi.org/10.1038/ng.3343
Dulak, A.M., et al. (2013) Exome and Whole Genome Sequencing of Esophageal Adeno-Carcinoma Identifies Recurrent Driver Events and Mutational Complexity. Nature Genetics, 45, 478-486. https://doi.org/10.1038/ng.2591
Bhardwaj, A., Stairs, D.B., Mani, H. and McGarrity, T.J. (2012) Barrett’s Esophagus: Emerging Knowledge and Management Strategies. Pathology Research International, 2012, Article ID: 814146. https://doi.org/10.1155/2012/814146
Bignold, L.P. (2005) Embryonic Reversions and Lineage Infidelities in Tumor Cells: Genome-Based Models and Role of Genetic Instability. International Journal of Experimental Pathology, 86, 67-79. https://doi.org/10.1111/j.0959-9673.2005.00421.x
Wong, D.J., Paulson, T.G., Prevo, L.J., Galipeau, P.C., Longton, G., Blount, P.L., et al. (2001) p16INK4a Lesions Are Common, Early Abnormalities That Undergo Clonal Expansion in Barrett’s Metaplastic Epithelium. Cancer Research, 61, 8284-8289.
Gorgoulis, V.G., Vassillou, L.-V.F., Karakaldos, P., Zacharatos, P., Kotsinas, A., Liloglou, T., et al. (2005) Activation of the DNA Damage Checkpoint and Genomic Instability in Human Precancerous Lesions. Nature, 434, 907-912. https://doi.org/10.1038/nature03485
Rubin, H., Yao, A. and Chow, M. (1995) Heritable, Population-Wide Damage to Cells as Driving Force of Neoplastic Transformation. Proceedings of the National Academy of Sciences of the United States of America, 92, 7734-7738. https://doi.org/10.1073/pnas.92.17.7734
Talbot, L.J., Bhattacharya, S.D. and Kuo, P.C. (2012) Epithelial-Mesenchymal Transition, the Tumor Microenvironment, and Metastatic Behavior of Epithelial Malignancies. International Journal of Biochemistry and Molecular Biology, 3, 117-136.
Klymkowsky, M.W. and Savagner, P. (2009) Epithelial-Mesenchymal Transition—A Cancer Researcher’s Conceptual Friend and Foe. The American Journal of Pathology, 174, 1588-1593. https://doi.org/10.2353/ajpath.2009.080545
Rohnalter, V., Roth, K., Finkernagel, F., Adhikary, T., Obert, J., Dorzweiler, K., et al. (2015) A Multi-Stage Process Including, Transient Polyploidization and EMT Precedes the Emergence of Chemoresistant Ovarian Carcinoma Cells with a Dedifferentiated and Pro-Inflammatory Secretory Phenotype. Oncotarget, 6, 40005-40025. https://doi.org/10.18632/oncotarget.5552
Turajlic, S. and Swanton, C. (2016) Metastasis as an Evolutionary Process. Science, 352, 169-175. https://doi.org/10.1126/science.aaf2784
White, E. and DiPaola, R.S. (2009) The Double-Edged Sword of Autophagy Modulation in Cancer. Clinical Cancer Research, 15, 5308-5316. https://doi.org/10.1158/1078-0432.CCR-07-5023
Peters, A.H., O’Caroll, D., Scherthan, H., Mechtler, K., Sauer, S., Schofer, C., et al. (2001) Loss of Suv39h Histone Methylation Transcription in Mammalian Heterochromatin and Genome Instability. Cell, 107, 323-337. https://doi.org/10.1016/S0092-8674(01)00542-6
Puig, P.E., Guilly, M.N., Bouchot, A., Droin, N., Cathelin, D., Bouyer, F., et al. (2008) Tumor Cell Can Escape DNA-Damaging Cisplatin through DNA Endoreduplication and Reversible Polyploidy. Cell Biology International, 32, 2031-2043. https://doi.org/10.1016/j.cellbi.2008.04.021
Wang, Q., Wu, P.C., Dong, D.Z., Ivanova, I., Chu, E., Zeliadi, S., Vesselle, H. and Wu, D.Y. (2013) Polyploidy Road to Therapy-Induced Cellular Senescence and Escape. International Journal of Cancer, 132, 1505-1515. https://doi.org/10.1002/ijc.27810
Mirzayans, R., Andrais, B., Kumar, P. and Murray, D. (2016) The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival? International Journal of Molecular Sciences, 17, 708. https://doi.org/10.3390/ijms17050708
Schwarzacher, H.G. and Schnedl, W. (1966) Position of Labelled Chromatids in Diplochromosomes of Endo-Reduplicated Cells after Uptake of Tritiated Thymidine. Nature, 209, 107-108. https://doi.org/10.1038/209107a0
Takanari, H., Nakakuki, K. and Izutsu, K. (1985) Cytogenetic Demonstration of Out-of-Phase DNA Synthesis in Endoreduplicated CHO Cells: Evidence for Partial Endoreduplication. Cytogenetics and Cell Genetics, 39, 93-98. https://doi.org/10.1159/000132114
Matsumoto, K. and Ohta, T. (1994) Chemical Induction of Quadruple and Octuple Chromosomes in Chinese Hamster CHO-K1 Cells and Relationship between Three-Dimensional Structure and Spatial Distribution of BrdU-Labeled Chromatids. Chromosoma, 103, 338-342. https://doi.org/10.1007/BF00417881
Levan, A. and Hauschka, T.S. (1953) Endomitotic Reduplication Mechanisms in Ascites Tumors of the Mouse. Journal of the National Cancer Institute, 14, 1-43.
Kuhn, E.M. (1981) A High Incidence of Mitotic Chiasma in Endoreduplicated Bloom’s Syndrome. Human Genetics, 58, 417-421. https://doi.org/10.1007/BF00282827
Davoli, T. and de Lange, T. (2011) The Causes and Consequences of Polyploidy in Normal Development and Cancer. Annual Review of Cell and Developmental Biology, 27, 585-610. https://doi.org/10.1146/annurev-cellbio-092910-154234
Collins, F.S. and Varmus, H. (2015) A New Initiative on Precision Medicine. The New England Journal of Medicine, 372, 793-795. https://doi.org/10.1056/NEJMp1500523
Malkin, D., Garber, J.E., Strong, L.C. and Friend, S.H. (2016) The Cancer Predisposition Revolution: How Was the Inherited Basis of Cancer Foreshadowed? Science, 352, 1052-1053. https://doi.org/10.1126/science.aag0832
Peifer, M., Fernandez-Cuesta, L., Sos, M.I., Geoge, J., Seidel, D., Kasper, L.H., Plenker, D., et al. (2012) Integrative Genome Analyses Identify Key Somatic Driver Mutations of Small-Cell Lung Cancer. Nature Genetics, 44, 1104-1112. https://doi.org/10.1038/ng.2396
Cerwenka, A. and Lanier, L.L. (2016) Natural Killers Join the Fight Against Cancer. Science, 359, 1416-1417.
Vosooughi, S., Roy, D. and Aral, S. (2018) The Spread of True and False News Online. Science, 359, 1146-1152. https://doi.org/10.1126/science.aap9559