Stem cells as common ancestors in a colorectal cancer ancestral tree.
OBJECTIVE
Cancer is thought to be an evolutionary process. Modern studies of evolution increasingly rely on genome comparisons, and similar molecular phylogeny approaches could be translated to somatic cell genomes to reconstruct colorectal cancer progression. The purpose of this review is to outline how human somatic cell ancestral trees can organize many old and new observations.


RESULTS
A somatic cell tree starts from the zygote and ends with present day normal or neoplastic cells. In between are ancestors and dead ends, which functionally correspond to stem and nonstem cells. Cancer genome projects illustrate that mutations are relatively infrequent, and consistent with normal mutation rates, particularly if mutations begin to accumulate from birth. Therefore, some mutations eventually found in cancers may first occur in normal appearing crypts, which are maintained by niches that allow for stem cell clonal evolution and selection. Although mutations occur too infrequently to function as somatic cell molecular clocks, potentially more labile epigenetic changes in CpG methylation may also record somatic cell ancestry.


CONCLUSIONS
Somatic cell evolution can occur throughout life, and potentially at least some of this unseen past may be reconstructed by 'reading' the lifetime changes that accumulate within our genomes.
Keck School of Medicine, Department of Pathology, University of Southern California, Los Angeles, California 90033, USA. dshibata@usc.edu
Darryl
D
Shibata
D001683:Biological Clocks / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002999:Clone Cells / Q000473:pathology / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D009154:Mutation; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*