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Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Many different tumor types have polyclonal tumor origin: evidence and implications
1Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, HFT-120, 3900 NCTR Road, USFDA, Jefferson, AR 72079, United States. barbara.parsons@fda.hhs.gov
Mutation Research
|July 11, 2008
Summary
Tumor growth may originate from multiple cells, not just one. New evidence suggests that many tumors, across various types, might arise from polyclonal origins, challenging long-held scientific beliefs.
Area of Science:
- Oncology
- Genetics
- Cancer Biology
Background:
- The monoclonal origin of tumors, where a tumor arises from a single cell, is a widely accepted scientific concept.
- This theory has persisted due to a lack of contradictory evidence and experimental challenges.
- X chromosome inactivation patch size data has historically supported the monoclonal origin hypothesis.
Purpose of the Study:
- To re-examine the established theory of monoclonal tumor origin.
- To present evidence supporting polyclonal tumor origin as a significant factor in cancer development.
- To explore the implications of polyclonal tumor origin for cancer risk assessment, modeling, and treatment.
Main Methods:
- Analysis of X-linked marker data, specifically X chromosome inactivation patch size, to assess tumor clonality.
- Utilizing chimeric models in rodents and humans to demonstrate tumor polyclonality.
- Examining mutational data, including oncogene and tumor suppressor gene mutations, in tumor tissues and normal tissues.
Main Results:
- X-linked marker data is more consistent with polyclonal tumor origin than monoclonal origin, with heterotypy observed in 24 tumor types.
- Chimeric models provided direct evidence of polyclonality in both rodent and human tumors.
- Mutational analysis revealed that initiated cells are more common than previously thought, and oncogenic mutations often exist as subpopulations within tumors.
Conclusions:
- The long-standing theory of monoclonal tumor origin needs re-evaluation.
- Polyclonal tumor origin, involving two or more interacting cells or clones, is a plausible explanation for many tumors.
- Understanding polyclonal tumor development is crucial for advancing cancer research, risk assessment, and therapeutic strategies.
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