Advanced

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

Gisselsson Nord, David LU (2011) In Advances in Cancer Research 112. p.1-9
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Advances in Cancer Research
volume
112
pages
1 - 9
publisher
Elsevier
external identifiers
  • WOS:000295818600001
  • PMID:21925299
  • Scopus:80052993287
ISSN
0065-230X
DOI
10.1016/B978-0-12-387688-1.00001-6
language
English
LU publication?
yes
id
f53f0c95-7df5-41bb-82d7-79c43f1c043a (old id 2168839)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21925299?dopt=Abstract
date added to LUP
2011-10-03 11:06:21
date last changed
2016-10-13 04:35:39
@misc{f53f0c95-7df5-41bb-82d7-79c43f1c043a,
  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 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.},
  author       = {Gisselsson Nord, David},
  issn         = {0065-230X},
  language     = {eng},
  pages        = {1--9},
  publisher    = {ARRAY(0x7ee02f0)},
  series       = {Advances in Cancer Research},
  title        = {Intratumor diversity and clonal evolution in cancer-a skeptical standpoint.},
  url          = {http://dx.doi.org/10.1016/B978-0-12-387688-1.00001-6},
  volume       = {112},
  year         = {2011},
}