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The clonal origin and clonal evolution of epithelial tumours
S B Garcia1, M Novelli, N A Wright
1Histopathology Unit, Imperial Cancer Research Fund, London, U.K.
International Journal of Experimental Pathology
|April 13, 2000
Summary
Tumor origin is often monoclonal, but some studies show multicellular origins. New in situ methods are needed to visualize clonal architecture in normal and cancerous tissues.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The origin of tumors, whether from a single cell or multiple cells, has long been a key question in experimental oncology.
- Recent advancements in molecular techniques have led to significant new insights into the clonal architecture of tumors and their precursors.
Purpose of the Study:
- To review and critically assess the evidence regarding the monoclonal origin of human tumors.
- To highlight limitations in current methodologies for determining tumor clonality.
- To explore the implications of clonal architecture in preneoplastic lesions.
Main Methods:
- Review of existing literature on tumor clonality and molecular techniques.
- Analysis of studies investigating the clonal origin of epithelial and other tumors.
- Consideration of factors like patch size and clonal evolution in clonality determination.
Main Results:
- Most studies support a monoclonal origin for human epithelial tumors, but exceptions exist.
- The impact of patch size and clonal evolution on clonality assessments has often been overlooked, confounding results.
- Preneoplastic lesions, including some hyperplasias, appear to be of clonal origin.
Conclusions:
- The assumption that a monoclonal origin invariably predicts a neoplastic phenotype requires re-evaluation.
- Current tissue disaggregation methods, even with microdissection, are suboptimal for studying clonal architecture.
- There is a need for improved in situ techniques to visualize the clonal architecture of normal tissues, preneoplastic lesions, and tumors.