Intratumor diversity and clonal evolution in cancer--a skeptical standpoint

Advances in Cancer Research
David Gisselsson

Abstract

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 relati...Continue Reading

Citations

Feb 19, 2013·Oncogene·S Yachida, C A Iacobuzio-Donahue
Dec 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Anders ValindDavid Gisselsson
May 6, 2015·ELife·Joshua M NicholsonDaniela Cimini
Jun 13, 2012·Journal of Cellular Biochemistry·Riccardo Di FioreRenza Vento
Jan 28, 2014·Biochemistry. Biokhimii︠a︡·T S GerashchenkoN V Cherdyntseva

Related Concepts

Autosome Abnormalities
Malignant Neoplasms
Genomic Stability
Somatic Evolution
Malignant Neoplasms
Cell Differentiation Process
Chromosomes
Biological Evolution
Genome
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