Clonal expansion in non-cancer tissues
- 24 February 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Cancer
- Vol. 21 (4), 239-256
- https://doi.org/10.1038/s41568-021-00335-3
Abstract
Cancer is a clonal disorder derived from a single ancestor cell and its progenies that are positively selected by acquisition of ‘driver mutations’. However, the evolution of positively selected clones does not necessarily imply the presence of cancer. On the contrary, it has become clear that expansion of these clones in phenotypically normal or non-cancer tissues is commonly seen in association with ageing and/or in response to environmental insults and chronic inflammation. Recent studies have reported expansion of clones harbouring mutations in cancer driver genes in the blood, skin, oesophagus, bronchus, liver, endometrium and bladder, where the expansion could be so extensive that tissues undergo remodelling of an almost entire tissue. The presence of common cancer driver mutations in normal tissues suggests a strong link to cancer development, providing an opportunity to understand early carcinogenic processes. Nevertheless, some driver mutations are unique to normal tissues or have a mutation frequency that is much higher in normal tissue than in cancer, indicating that the respective clones may not necessarily be destined for evolution to cancer but even negatively selected for carcinogenesis depending on the mutated gene. Moreover, tissues that are remodelled by genetically altered clones might define functionalities of aged tissues or modified inflammatory processes. In this Review, we provide an overview of major findings on clonal expansion in phenotypically normal or non-cancer tissues and discuss their biological significance not only in cancer development but also in ageing and inflammatory diseases.Keywords
This publication has 189 references indexed in Scilit:
- DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegiseLife, 2013
- The Origin and Evolution of Mutations in Acute Myeloid LeukemiaCell, 2012
- The human urothelium consists of multiple clonal units, each maintained by a stem cellThe Journal of Pathology, 2011
- Clonal architecture of human prostatic epithelium in benign and malignant conditionsThe Journal of Pathology, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- The histogenesis of regenerative nodules in human liver cirrhosisJournal of Hepatology, 2009
- Epidermal Notch1 Loss Promotes Skin Tumorigenesis by Impacting the Stromal MicroenvironmentCancer Cell, 2009
- A Methodological Approach to Tracing Cell Lineage in Human Epithelial TissuesThe International Journal of Cell Cloning, 2009
- Analysis of the clonal architecture of the human small intestinal epithelium establishes a common stem cell for all lineages and reveals a mechanism for the fixation and spread of mutationsThe Journal of Pathology, 2009
- RNA Editing Enzyme APOBEC1 and Some of Its Homologs Can Act as DNA MutatorsMolecular Cell, 2002