Cited by 6,471Cancer Genomics and DiagnosticsCancer Cells and MetastasisEvolution and Genetic Dynamics

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The Clonal Evolution of Tumor Cell Populations: Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression.

Nowell, Peter C.·1976·Science

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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.

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Authors: Nowell, P. C.
Affiliations: School of Medicine, University of Pennsylvania, Philadelphia 19174.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1976-10
Volume: 194
Issue: 4260
Pages: 23-28
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.959840
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

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The Clonal Evolution of Tumor Cell Populations: Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression.

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