Intratumor diversity and clonal evolution in cancer-a skeptical standpoint.
Author
Summary, in English
Clonal evolution in cancer is intimately linked to the concept of intratumor cellular diversity, as the latter is a prerequisite for Darwinian selection at the micro-level. It has been frequently suggested in the literature that clonal evolution can be promoted by an elevated rate of mutation in tumor cells, so-called genomic instability, the mechanisms of which are now becoming increasingly well characterized. However, several issues need clarification before the presumably complex relationship between mutation rate, intratumor diversity, and clonal evolution can be understood sufficiently well to translate into models that predict the course of tumor disease. In particular, it has to be clarified which of the proposed mechanisms for genomic instability that are able to generate daughter cells with sufficient viability to form novel clones, how clones with different genomic changes differ phenotypically from each other, and what the selective forces are that guide competition among diverse clones in different microenvironments. Furthermore, standardized measurements of mutation rates at the chromosome level, as well as genotypic and phenotypic diversity, are essential to compare data from different studies. Finally, the relationship between clonal variation brought about by genomic instability, on the one hand, and cellular differentiation hierarchies, on the other hand, should be explored to put genomic instability in the context of the tumor stem cell hypothesis.
Department/s
- Division of Clinical Genetics
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2011
Language
English
Pages
1-9
Publication/Series
Advances in Cancer Research
Volume
112
Links
Document type
Journal article
Publisher
Elsevier
Topic
- Medical Genetics
Status
Published
ISBN/ISSN/Other
- ISSN: 0065-230X