The Clonal Evolution of Tumor Cell Populations: Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression.
Abstract
It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mutations enabling rapid proliferation are selected positively in cancers because they accelerate the emergence of aggressive phenotypes through somatic evolution.
“Mutations enabling rapid proliferation are selected positively in cancers because they accelerate the emergence of aggressive phenotypes through somatic evolution.1,2”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [2]
Cites
Mutation selection and the natural history of cancer
Cairns, J. (1975) · Nature · doi:10.1038/255197a0 · Cited by 1,592 · see citing works
Normal genetically mosaic mice produced from malignant teratocarcinoma cells.
Mintz, B., & Illmensee, K. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.9.3585 · Cited by 1,179 · see citing works
Handbuch der allgemeinen pathologie
(1973) · Experimental Gerontology · doi:10.1016/0531-5565(73)90021-1 · Cited by 794 · see citing works
Glucose-6-Phosphate Dehydrogenase Mosaicism: Utilization as a Cell Marker in the Study of Leiomyomas
Linder, D., & Gartler, S. M. (1965) · Science · doi:10.1126/science.150.3692.67 · Cited by 398 · see citing works
Differentiation of malignant to benign cells
Kauffman, S. A. (1971) · Journal of Theoretical Biology · doi:10.1016/0022-5193(71)90020-8 · Cited by 309 · see citing works
Suppression of malignancy in human cells
Stanbridge, E. J. (1976) · Nature · doi:10.1038/260017a0 · Cited by 307 · see citing works
Methodology in mammalian genetics
Burdette, W. J. (1963) · Holden-Day eBooks · doi:10.5962/bhl.title.6428 · Cited by 302 · see citing works
LEVAN, A., Levan, G., & Mitelman, F. (2009) · Hereditas · doi:10.1111/j.1601-5223.1977.tb01208.x · Cited by 263 · see citing works
The analysis of malignancy by cell fusion: I. hybrids between tumour cells and l cell derivatives
Klein, G., Bregula, U., Wiener, F., & Harris, H. (1971) · Journal of Cell Science · doi:10.1242/jcs.8.3.659 · Cited by 248 · see citing works
Neoplasia: a disease of cell differentiation.
Markert, C. L. (1968) · PubMed · Cited by 244 · see citing works
ROLE OF CHROMOSOMES IN CANCEROGENESIS, AS STUDIED IN SERIAL TISSUE CULTURE OF MAMMALIAN CELLS
LEVAN, A., & Biesele, J. J. (1958) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1958.tb54666.x · Cited by 219 · see citing works
Teebor, G. W., & Becker, F. F. (1971) · PubMed · Cited by 219 · see citing works
Mechanism of Cell Transformation by RNA Tumor Viruses
Temin, H. M. (1971) · Annual Review of Microbiology · doi:10.1146/annurev.mi.25.100171.003141 · Cited by 216 · see citing works
The Origin and Development of Human Tumors Studied with Cell Markers
Fialkow, P. J. (1974) · New England Journal of Medicine · doi:10.1056/nejm197407042910109 · Cited by 207 · see citing works
Clustering of aberrations to specific chromosomes in human neoplasms
Levan, G., & Mitelman, F. (2009) · Hereditas · doi:10.1111/j.1601-5223.1975.tb01474.x · Cited by 206 · see citing works
Cancer, Differentiation and Embryonic Antigens: Some Central Problems
Coggin, J. H., & Anderson, N. G. (1974) · Advances in cancer research · doi:10.1016/s0065-230x(08)60053-6 · Cited by 184 · see citing works
The chromosomes in ontogeny and oncogeny.
Hauschka, T. S. (1961) · PubMed · Cited by 175 · see citing works
Carcinogens, Enzyme Induction, and Gene Action
Gelboin, H. V. (1967) · Advances in cancer research · doi:10.1016/s0065-230x(08)60076-7 · Cited by 173 · see citing works
RELATIONSHIPS OF VIRUSES, CHROMOSOMES AND CARCINOGENESIS
Nichols, W. W. (2009) · Hereditas · doi:10.1111/j.1601-5223.1963.tb01894.x · Cited by 166 · see citing works
Chromosomal Evolution in Cell Populations
Hsü, T. C. (1962) · International review of cytology · doi:10.1016/s0074-7696(08)60539-2 · Cited by 157 · see citing works
Carcinogenesis--cellular evolution as a unifying thread: Presidential address.
Farber, E. (1973) · PubMed · Cited by 150 · see citing works
Chromosomal Abnormalities in Human Neoplasia
Sandberg, A. A., & Hossfeld, D. K. (1970) · Annual Review of Medicine · doi:10.1146/annurev.me.21.020170.002115 · Cited by 146 · see citing works
Tumor Etiology and Chromosome Pattern
Mitelman, F., Mark, J., Levan, G., & LEVAN, A. (1972) · Science · doi:10.1126/science.176.4041.1340 · Cited by 145 · see citing works
Nonrandom chromosomal abnormalities in hematologic disorders of man.
Rowley, J. D. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.1.152 · Cited by 139 · see citing works
Chromosomes of "minimal deviation" hepatomas and some other transplantable rat tumors.
Nowell̀, P. C., Morris, H. P., & Potter, V. R. (1967) · PubMed · Cited by 117 · see citing works
Self-citationAssignment of the T-Antigen Gene of Simian Virus 40 to Human Chromosome C-7
Croce, C. M., Girardi, A. J., & Koprowski, H. (1973) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.70.12.3617 · Cited by 115 · see citing works
Identification of the Chromosomes that Control Malignancy
Yamamoto, T., Rabinowitz, Z., & Sachs, L. (1973) · Nature New Biology · doi:10.1038/newbio243247a0 · Cited by 105 · see citing works
Ryser, H. J. ‐. (1971) · New England Journal of Medicine · doi:10.1056/nejm197109232851305 · Cited by 103 · see citing works
Chromosome aberrations in cultured cells deprived of single essential amino acids
Freed, J. J., & Schatz, S. A. (1969) · Experimental Cell Research · doi:10.1016/0014-4827(69)90574-6 · Cited by 97 · see citing works
Genetic implication of karyological instability of malignant somatic cells
Ono, S. (1971) · Physiological Reviews · doi:10.1152/physrev.1971.51.3.496 · Cited by 83 · see citing works
Cellular membranes and tumor behavior: a new hypothesis.
Wallach, D. F. H. (1968) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.61.3.868 · Cited by 82 · see citing works
Parrington, J. M., Delhanty, J. D. A., & Baden, H. P. (1971) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1956.tb01387.x · Cited by 81 · see citing works
Radiation Carcinogenesis: The Sequence of Events
Cole, L. J., & Nowell̀, P. C. (1965) · Science · doi:10.1126/science.150.3705.1782 · Cited by 70 · see citing works
Self-citationWiener, F., Klein, G., & Harris, H. (1973) · Journal of Cell Science · doi:10.1242/jcs.12.1.253 · Cited by 70 · see citing works
Chromosomes and causation of human cancer and leukemia. II. Karyotypes of human solid tumors
Yamada, K., Takagi, N., & Sandberg, A. A. (1966) · Cancer · doi:10.1002/1097-0142(196612)19:12 · Cited by 57 · see citing works
Chromosome Banding Studies in Acute Leukaemia at Diagnosis
Lawler, S. D., Secker‐Walker, L. M., Summersgill, B. M., Reeves, B. R., Lewis, J. P., Kay, H. E. M., & Hardisty, R. M. (1975) · Scandinavian Journal of Haematology · doi:10.1111/j.1600-0609.1975.tb01086.x · Cited by 51 · see citing works
Chromosome Studies of Virus-Induced Rabbit Papillomas and Derived Primary Carcinomas
McMichael, H., Wagner, J. E., Nowell̀, P. C., & Hungerford, D. A. (1963) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/31.5.1197 · Cited by 37 · see citing works
Self-citationStudies on the Variability of Immunoglobulin SequencePreprint
Milstein, C., Frangione, B., & Pink, J. R. L. (1967) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1967.032.01.007 · Cited by 35 · see citing works
Viral “Tumorigenesis” in man: Cell markers in condylomata acuminata
Friedman, J. M., & Fialkow, P. J. (1976) · International Journal of Cancer · doi:10.1002/ijc.2910170109 · Cited by 34 · see citing works
A Chromosomal Theory of Carcinogenesis
GROUCHY, J. D., & NAVA, C. D. (1968) · Annals of Internal Medicine · doi:10.7326/0003-4819-69-2-381 · Cited by 33 · see citing works
Human Lymphoblastoid Cell Lines. II. Cytogenetic Studies
Steel, C. M., McBeath, S., & O'Riordan, M. L. (1971) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/47.6.1203 · Cited by 27 · see citing works
Reversible appearance of a specific chromosome which suppresses malignancy
Codish, S. D., & Paul, B. (1974) · Nature · doi:10.1038/252610a0 · Cited by 27 · see citing works
Wiener, F., Dalianis, T., Klein, G., & Harris, H. (1974) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/52.6.1779 · Cited by 23 · see citing works
Harris, M. (1974) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/52.6.1811 · Cited by 22 · see citing works
Further Studies on Karyotypes of a Variety of Primary and Transplanted Mouse Polyoma Tumors 2
Hellström, K. E., Hellström, I., & Sjögren, H. O. (1963) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/31.5.1239 · Cited by 18 · see citing works
AlSaadi, A. A., & Beierwaltes, W. H. (1967) · PubMed · Cited by 18 · see citing works
RELATION BETWEEN CHROMOSOMAL ALTERATION AND DEVELOPMENT OF TUMORS
YOSIDA, T. H. (1966) · The Japanese Journal of Genetics · doi:10.1266/jjg.41.439 · Cited by 9 · see citing works
Lovvorn, R. L. (1976) · Science · doi:10.1126/science.191.4224.241 · Cited by 9 · see citing works
Mark, J. (1971) · Acta Pathologica Microbiologica Scandinavica Section A Pathology · doi:10.1111/j.1699-0463.1971.tb03327.x · Cited by 5 · see citing works
Lovvorn, R. L. (1976) · Science · doi:10.1126/science.191.4224.241.a · Cited by 5 · see citing works
Is there another approach to cancer therapy?--Workshop on suppression of the malignant phenotype.
Stansly, P. G. (1975) · PubMed · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
A genetic model for colorectal tumorigenesis
Fearon, E. R., & Vogelstein, B. (1990) · Cell · doi:10.1016/0092-8674(90)90186-i · Cited by 12,132 · see citing works
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · see citing works
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841 · see citing works
The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited
Fidler, I. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1098 · Cited by 4,686 · see citing works
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017 · see citing works
Tumour heterogeneity and resistance to cancer therapies
Dagogo-Jack, I., & Shaw, A. T. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.166 · Cited by 3,846 · see citing works
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531 · see citing works
Cancer stem cells in solid tumours: accumulating evidence and unresolved questions
Visvader, J., & Lindeman, G. (2008) · Nature Reviews. Cancer · doi:10.1038/nrc2499 · Cited by 3,562 · see citing works
Immunogenic cell death and DAMPs in cancer therapy
Krysko, D. V., Garg, A. D., Kaczmarek, A., Krysko, O., Agostinis, P., & Vandenabeele, P. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3380 · Cited by 3,223 · see citing works
Greaves, M., & Maley, C. C. (2012) · Nature · doi:10.1038/nature10762 · Cited by 3,162 · see citing works
Emerging Biological Principles of Metastasis
Lambert, A. W., Pattabiraman, D. R., & Weinberg, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.11.037 · Cited by 3,075 · see citing works
Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability
Colotta, F., Allavena, P., Sica, A., Garlanda, C., & Mantovani, A. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp127 · Cited by 2,882 · see citing works
A view on drug resistance in cancer
Vasan, N., Baselga, J., & Hyman, D. M. (2019) · Nature · doi:10.1038/s41586-019-1730-1 · Cited by 2,770 · see citing works
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840 · see citing works
Hsieh, J. J.-D., Purdue, M. P., Signoretti, S., Swanton, C., Albiges, L. K., Schmidinger, M., Heng, D. Y. C., Larkin, J., & Ficarra, V. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.9 · Cited by 2,797 · see citing works
Tumour evolution inferred by single-cell sequencing
Navin, N., Kendall, J., Troge, J., Andrews, P., Rodgers, L., McIndoo, J., Cook, K., Stepansky, A., Levy, D., Esposito, D., et al. (2011) · Nature · doi:10.1038/nature09807 · Cited by 2,598 · see citing works
Roodman, G. D. (2004) · New England Journal of Medicine · doi:10.1056/nejmra030831 · Cited by 2,752 · see citing works
Hartwell, L. H., & Kastan, M. B. (1994) · Science · doi:10.1126/science.7997877 · Cited by 2,523 · see citing works
Plasminogen Activators, Tissue Degradation, and Cancer
Danø, K., Andreasen, P. A., Grøndahl-Hansen, J., Kristensen, P., Nielsen, L. S., & Skriver, L. (1985) · Advances in cancer research · doi:10.1016/s0065-230x(08)60028-7 · Cited by 2,535 · see citing works
Genomic instability — an evolving hallmark of cancer
Negrini, S., Gorgoulis, V. G., & Halazonetis, T. D. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2858 · Cited by 2,397 · see citing works
Tumour heterogeneity and cancer cell plasticity
Meacham, C., & Morrison, S. (2013) · Nature · doi:10.1038/nature12624 · Cited by 2,350 · see citing works
The causes and consequences of genetic heterogeneity in cancer evolution
Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013) · Nature · doi:10.1038/nature12625 · Cited by 2,262 · see citing works
Evolution of the Cancer Stem Cell Model
Kreso, A., & Dick, J. E. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.006 · Cited by 2,212 · see citing works
TRANSFORMING GROWTH FACTOR-β REGULATION OF IMMUNE RESPONSES
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A.-K. L., & Flavell, R. A. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090737 · Cited by 2,199 · see citing works
Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry
Giesen, C., Wang, H. A. O., Schapiro, D., Zivanovic, N., Jacobs, A., Hattendorf, B., Schüffler, P. J., Grolimund, D., Buhmann, J. M., Brandt, S., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2869 · Cited by 1,951 · see citing works
Intra-tumour heterogeneity: a looking glass for cancer?
Marusyk, A., Almendro, V., & Polyák, K. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3261 · Cited by 2,003 · see citing works
Merlo, A., Herman, J. G., Mao, L., Lee, D. J., Gabrielson, E. W., Burger, P. C., Baylin, S. B., & Sidransky, D. (1995) · Nature Medicine · doi:10.1038/nm0795-686 · Cited by 1,978 · see citing works
Alterations in DNA Methylation: A Fundamental Aspect of Neoplasia
Baylln, S. B., Herman, J. G., Graff, J. R., Vertino, P. M., & Issa, J. J. (1997) · Advances in cancer research · doi:10.1016/s0065-230x(08)60702-2 · Cited by 1,913 · see citing works
The cancer stem cell: premises, promises and challenges
Clevers, H. (2011) · Nature Medicine · doi:10.1038/nm.2304 · Cited by 1,915 · see citing works
High burden and pervasive positive selection of somatic mutations in normal human skin
Martincorena, I., Roshan, A., Gerstung, M., Ellis, P., Van Loo, P., McLaren, S., Wedge, D. C., Fullam, A., Alexandrov, L. B., Tubio, J. M., et al. (2015) · Science · doi:10.1126/science.aaa6806 · Cited by 1,770 · see citing works
The multistep nature of cancer
Vogelstein, B., & Kinzler, K. W. (1993) · Trends in Genetics · doi:10.1016/0168-9525(93)90209-z · Cited by 1,858 · see citing works
The pathogenesis of cancer metastasis
Poste, G. H., & Fidler, I. J. (1980) · Nature · doi:10.1038/283139a0 · Cited by 1,739 · see citing works
Identification of a Chromosome 18q Gene that Is Altered in Colorectal Cancers
Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., et al. (1990) · Science · doi:10.1126/science.2294591 · Cited by 1,738 · see citing works
Addiction to Oncogenes--the Achilles Heal of Cancer
Weinstein, I. (2002) · Science · doi:10.1126/science.1073096 · Cited by 1,753 · see citing works
Universal Patterns of Selection in Cancer and Somatic Tissues
Martincorena, I., Raine, K. M., Gerstung, M., Dawson, K. J., Haase, K., Van Loo, P., Davies, H., Stratton, M. R., & Campbell, P. J. (2017) · Cell · doi:10.1016/j.cell.2017.09.042 · Cited by 1,523 · see citing works
Cancer as an evolutionary and ecological process
Merlo, L. M. F., Pepper, J. W., Reid, B. J., & Maley, C. C. (2006) · Nature reviews. Cancer · doi:10.1038/nrc2013 · Cited by 1,690 · see citing works
Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer
Beltran, H., Prandi, D., Mosquera, J. M., Benelli, M., Puca, L., Cyrta, J., Marotz, C. A., Γιαννοπούλου, Ε., Chakravarthi, B. V. S. K., Varambally, S., et al. (2016) · Nature Medicine · doi:10.1038/nm.4045 · Cited by 1,669 · see citing works
Immune evasion in cancer: mechanistic basis and therapeutic strategies
Vinay, D. S., Ryan, E. P., Pawelec, G., Talib, W. H., Stagg, J., Elkord, E., Lichtor, T., Decker, W. K., Whelan, R. L., Kumara, H. M. C. S., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.004 · Cited by 1,625 · see citing works
Tumor heterogeneity: Causes and consequences
Marusyk, A., & Polyák, K. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2009.11.002 · Cited by 1,597 · see citing works
The origin and evolution of mutations in acute myeloid leukemia
Welch, J. S., Ley, T. J., Link, D. C., Miller, C. A., Larson, D. E., Koboldt, D. C., Wartman, L. D., Lamprecht, T. L., Liu, F., Xia, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.023 · Cited by 1,575 · see citing works
Endogenous DNA damage as a source of genomic instability in cancer
Tubbs, A., & Nussenzweig, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.002 · Cited by 1,452 · see citing works
Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403 · see citing works
A mechanism linking extra centrosomes to chromosomal instability
Ganem, N. J., Godinho, S. A., & Pellman, D. S. (2009) · Nature · doi:10.1038/nature08136 · Cited by 1,427 · see citing works
Metastasis Results from Preexisting Variant Cells Within a Malignant Tumor
Fidler, I. J., & Kripke, M. L. (1977) · Science · doi:10.1126/science.887927 · Cited by 1,426 · see citing works
Somatic mutation in cancer and normal cells
Martincorena, I., & Campbell, P. J. (2015) · Science · doi:10.1126/science.aab4082 · Cited by 1,396 · see citing works
The impact of translocations and gene fusions on cancer causation
Mitelman, F., Johansson, B., & Mertens, F. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2091 · Cited by 1,400 · see citing works
The evolutionary history of lethal metastatic prostate cancer
ICGC Prostate UK Group, Gundem, G., Loo, P. V., Kremeyer, B., Alexandrov, L. B., Tubío, J. M. C., Papaemmanuil, E., Brewer, D. S., Kallio, H. M. L., Högnäs, G., et al. (2015) · Nature · doi:10.1038/nature14347 · Cited by 1,358 · see citing works
Tumor Microsatellite Instability and Clinical Outcome in Young Patients with Colorectal Cancer
Gryfe, R., Kim, H., Hsieh, E., Aronson, M. D., Holowaty, E. J., Bull, S. B., Redston, M. S., & Gallinger, S. (2000) · New England Journal of Medicine · doi:10.1056/nejm200001133420201 · Cited by 1,378 · see citing works
Jass, J. R. (2006) · Histopathology · doi:10.1111/j.1365-2559.2006.02549.x · Cited by 1,381 · see citing works
Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53
Livingstone, L. R., White, A., Sprouse, J., Livanos, E., Jacks, T., & Tlsty, T. D. (1992) · Cell · doi:10.1016/0092-8674(92)90243-6 · Cited by 1,333 · see citing works
Lessons from the Cancer Genome
Garraway, L. A., & Lander, E. S. (2013) · Cell · doi:10.1016/j.cell.2013.03.002 · Cited by 1,322 · see citing works
Cancer stem cells: current status and evolving complexities.
Visvader, J., & Lindeman, G. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.05.007 · Cited by 1,299 · see citing works
Tumour heterogeneity in the clinic
Bedard, P. L., Hansen, A. R., Ratain, M. J., & Siu, L. L. (2013) · Nature · doi:10.1038/nature12627 · Cited by 1,214 · see citing works
Braakhuis, B. J. M., Tabor, M. P., Kummer, J. A., Leemans, C. R., & Brakenhoff, R. H. (2003) · PubMed · Cited by 1,208 · see citing works
On the Origin of Cancer Metastasis
Seyfried, T. N., & Huysentruyt, L. C. (2012) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.v18.i1-2.40 · Cited by 1,192 · see citing works
AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective
Talmadge, J. E., & Fidler, I. J. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1040 · Cited by 1,172 · see citing works
Heterogeneity in Cancer: Cancer Stem Cells versus Clonal Evolution
Shackleton, M. J., Quintana, E., Fearon, E. R., & Morrison, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.08.017 · Cited by 1,152 · see citing works
Ovarian cancer: strategies for overcoming resistance to chemotherapy
Agarwal, R., & Kaye, S. B. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1123 · Cited by 1,155 · see citing works
The evolutionary history of 2,658 cancers
Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., Mitchell, T. J., Rubanova, Y., Anur, P., Yu, K., et al. (2020) · Nature · doi:10.1038/s41586-019-1907-7 · Cited by 1,057 · see citing works
Biological and therapeutic impact of intratumor heterogeneity in cancer evolution
McGranahan, N., & Swanton, C. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.12.001 · Cited by 1,077 · see citing works
Cancer stem cells: impact, heterogeneity, and uncertainty
Magee, J. A., Piskounova, E., & Morrison, S. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.03.003 · Cited by 1,137 · see citing works
Lung cancer: Biology and treatment options
Lemjabbar‐Alaoui, H., Hassan, O. U., Yang, Y., & Buchanan, P. C. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.08.002 · Cited by 1,024 · see citing works
T and Tn, General Carcinoma Autoantigens
Springer, G. F. (1984) · Science · doi:10.1126/science.6729450 · Cited by 1,009 · see citing works
PyClone: statistical inference of clonal population structure in cancer
Roth, A. J. L., Khattra, J. S., Yap, D., Wan, A. N. C., Laks, E., Biele, J., Ha, G., Aparicio, S. A. J. R., Bouchard‐Côté, A., & Shah, S. P. (2014) · Nature Methods · doi:10.1038/nmeth.2883 · Cited by 1,002 · see citing works
Cancer heterogeneity: implications for targeted therapeutics
Fisher, R. A., Pusztai, L., & Swanton, C. (2013) · British Journal of Cancer · doi:10.1038/bjc.2012.581 · Cited by 980 · see citing works
Intratumor Heterogeneity: Evolution through Space and Time
Swanton, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2217 · Cited by 931 · see citing works
DePinho, R. A. (2000) · Nature · doi:10.1038/35041694 · Cited by 951 · see citing works
Tumor microenvironmental physiology and its implications for radiation oncology
Vaupel, P. W. (2004) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2004.04.008 · Cited by 948 · see citing works
A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity.
Nishikawa, R., Ji, X.-D., Harmon, R. C., Lazar, C. S., Gill, G. N., Cavenee, W. K., & Huang, H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7727 · Cited by 936 · see citing works
Biological Diversity in Metastatic Neoplasms: Origins and Implications
Fidler, I. J., & Hart, I. R. (1982) · Science · doi:10.1126/science.7112116 · Cited by 926 · see citing works
Cancer Epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance
Easwaran, H., Tsai, H.-C., & Baylin, S. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.015 · Cited by 915 · see citing works
DNA Mismatch Repair: Functions and Mechanisms
Iyer, R. R., Pluciennik, A., Burdett, V., & Modrich, P. L. (2005) · Chemical Reviews · doi:10.1021/cr0404794 · Cited by 906 · see citing works
Rausch, T., Jones, D. T. W., Zapatka, M., Stütz, A. M., Zichner, T., Weischenfeldt, J., Jäger, N., Remke, M., Shih, D., Northcott, P. A., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.013 · Cited by 865 · see citing works
Evolution of high mutation rates in experimental populations of E. coli
Sniegowski, P. D., Gerrish, P. J., & Lenski, R. E. (1997) · Nature · doi:10.1038/42701 · Cited by 879 · see citing works
c-Myc Can Induce DNA Damage, Increase Reactive Oxygen Species, and Mitigate p53 Function
Vafa, O., Wade, M., Kern, S., Beeche, M., Pandita, T. K., Hampton, G. M., & Wahl, G. M. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00520-8 · Cited by 876 · see citing works
Cancer Stem Cells: Basic Concepts and Therapeutic Implications
Nassar, D., & Blanpain, C. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044438 · Cited by 869 · see citing works
Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity
Turner, K. M., Deshpande, V., Beyter, D., Koga, T., Rusert, J. M., Lee, C., Li, B., Arden, K. C., Ren, B., Nathanson, D. A., et al. (2017) · Nature · doi:10.1038/nature21356 · Cited by 852 · see citing works
Tumour-initiating cells: challenges and opportunities for anticancer drug discovery
Zhou, B. S., Zhang, H., Damelin, M. I., Geles, K. G., Grindley, J. C., & Dirks, P. B. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2137 · Cited by 834 · see citing works
Tumour evolution in hepatocellular carcinoma
Craig, A. J., von Felden, J., García‐Lezana, T., Sarcognato, S., & Villanueva, A. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0229-4 · Cited by 825 · see citing works
Tumor heterogeneity and the biology of cancer invasion and metastasis.
Fidler, I. J. (1978) · PubMed · Cited by 818 · see citing works
Genetic variegation of clonal architecture and propagating cells in leukaemia
Anderson, K., Lutz, C., van Delft, F. W., Bateman, C. M., Guo, Y., Colman, S., Kempski, H. M., Moorman, A. V., Titley, I., Swansbury, J. G., et al. (2010) · Nature · doi:10.1038/nature09650 · Cited by 803 · see citing works
The Biology of Cancer Invasion and Metastasis
Fidler, I. J., Gersten, D. M., & Hart, I. R. (1978) · Advances in cancer research · doi:10.1016/s0065-230x(08)60648-x · Cited by 802 · see citing works
Genetic determinants of cancer metastasis
Nguyen, D. X., & Massagué, J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2101 · Cited by 796 · see citing works
DNA repair, genome stability and cancer: a historical perspective
Jeggo, P. A., Pearl, L. H., & Carr, A. M. (2015) · Nature reviews. Cancer · doi:10.1038/nrc.2015.4 · Cited by 764 · see citing works
Pan-cancer analysis of the extent and consequences of intratumor heterogeneity
Andor, N., Graham, T. A., Jansen, M., Xia, L. C., Aktipis, A., Petritsch, C. K., Ji, H. P., & Maley, C. C. (2015) · Nature Medicine · doi:10.1038/nm.3984 · Cited by 752 · see citing works
Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells
Hartwell, L. H. (1992) · Cell · doi:10.1016/0092-8674(92)90586-2 · Cited by 770 · see citing works
Loeb, L. A., Loeb, K. R., & Anderson, J. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0334858100 · Cited by 762 · see citing works
Clonal evolution of glioblastoma under therapy
Wang, J., Cazzato, E., Ladewig, E., Frattini, V., Rosenbloom, D. I. S., Zairis, S., Abate, F., Liu, Z., Elliott, O., Shin, Y., et al. (2016) · Nature Genetics · doi:10.1038/ng.3590 · Cited by 759 · see citing works
Tumor Morphology and Phenotypic Evolution Driven by Selective Pressure from the Microenvironment
Anderson, A. R. A., Weaver, A. M., Cummings, P. T., & Quaranta, V. (2006) · Cell · doi:10.1016/j.cell.2006.09.042 · Cited by 757 · see citing works
Genetic instability and darwinian selection in tumours
Cahill, D. P., Kinzler, K. W., Vogelstein, B., & Christoph Lengauer, C. (1999) · Trends in Cell Biology · doi:10.1016/s0962-8924(99)01661-x · Cited by 747 · see citing works
How nucleotide excision repair protects against cancer
Friedberg, E. C. (2001) · Nature Reviews Cancer · doi:10.1038/35094000 · Cited by 730 · see citing works
Rajagopalan, H., & Christoph Lengauer, C. (2004) · Nature · doi:10.1038/nature03099 · Cited by 730 · see citing works
A microenvironmental model of carcinogenesis
Gatenby, R. A., & Gillies, R. J. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2255 · Cited by 725 · see citing works
Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity
Vermeulen, L., Todaro, M., Melo, F. D. S. E., Sprick, M. R., Kemper, K., Pérez‐Alea, M., Richel, D. J., Stassi, G., & Medema, J. P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805706105 · Cited by 725 · see citing works
Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia
Jan, M., Snyder, T. M., Corces-Zimmerman, M. R., Vyas, P., Weissman, I. L., Quake, S. R., & Majeti, R. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004315 · Cited by 721 · see citing works
Defining the mode of tumour growth by clonal analysis
Driessens, G., Beck, B., Caauwe, A., Simons, B. D., & Blanpain, C. (2012) · Nature · doi:10.1038/nature11344 · Cited by 718 · see citing works
Defining the Hallmarks of Metastasis
Welch, D. R., & Hurst, D. R. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0458 · Cited by 695 · see citing works
Genetic clonal diversity predicts progression to esophageal adenocarcinoma
Maley, C. C., Galipeau, P. C., Finley, J. C., Wongsurawat, V. J., Li, X., Sanchez, C. A., Paulson, T. G., Blount, P. L., Risques, R., Rabinovitch, P. S., et al. (2006) · Nature Genetics · doi:10.1038/ng1768 · Cited by 687 · see citing works
Lanman, R. B., Mortimer, S. A., Zill, O. A., Sebisanovic, D., Lopez, R., Blau, S., Collisson, E. A., Divers, S. G., Hoon, D. S. B., Kopetz, E. S., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140712 · Cited by 695 · see citing works
“Peter Nowell posited almost 40 years ago that “each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline [subclone] resistant to the treatment” [62].”
Background
- Authors
- Nowell, P. C.
- Affiliations
- School of Medicine, University of Pennsylvania, Philadelphia 19174.
- Venue
- Science
- Published
- 1976-10
- Volume
- 194
- Issue
- 4260
- Pages
- 23-28
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1967304777
- Cited by
- 6,471
- References
- 52
- Citations by year
- 2026: 117 · 2025: 163 · 2024: 183 · 2023: 201 · 2022: 209 · 2021: 282 · 2020: 287 · 2019: 259 · 2018: 304 · 2017: 332 · 2016: 263 · 2015: 261 · 2014: 241 · 2013: 233 · 2012: 200
- FWCI
- 16.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- clonal evolution, tumor progression, karyotypic heterogeneity, tumor cell populations, treatment resistance, carcinogen exposure, precision oncology
- MeSH terms
- Carcinogens, Chromosomes, Clone Cells, Karyotyping, Models, Biological, Mutation, Neoplasms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
