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Discovering the causes of cancer and the means of prevention
 

Normal tissue mutational landscapes and cancer risk

Headshot of Dr. Phil Jones of the University of Cambridge

June 30, 2022 | 10:30 AM – 11:30 AM

Online via Webex

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Speaker:

Dr. Phil Jones
Professor
Cancer Development
University of Cambridge
MRC Cancer Unit

Abstract:

Aging normal tissues are colonized by clones carrying mutant genes under strong positive selection. In aging squamous epithelia, the majority of cells carry mutations associated with cancer, but tumor formation is comparatively rare.  This observation may be explained by the presence of mutants that are highly competitive in normal tissue, such as NOTCH1 in the esophagus, but which may suppress tumors by displacing microscopic lesions from the epithelium and retarding the growth of established lesions.  Conversely, the progression of oncogenic p53 mutants is constrained by a bottleneck in normal epithelium, as loss of the second allele does not increase competitive fitness, so such clones are likely to be lost by neutral competition.  Understanding the clonal dynamics and properties of pro- and anti-oncogenic mutants will be key to understanding the relationship between the complex mutational landscapes of aging tissues and cancer risk.

Host:

Mark Little, D.Phil.
Senior Investigator
Radiation Epidemiology Branch
DCEG 

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