Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either generation of induced pluripotent stem cells, or sequencing of single-cell genomes, are inherently error-prone and do not allow independent validation of the mutations.
In the attached article, authors ingeniously eliminated these potential sources of error by high-coverage genome sequencing of single-cell-derived clonal fibroblast lineages, obtained after minimal propagation in culture––prepared from skin biopsies of two healthy adult humans. They describe the accurate measurements of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. Authors found that every cell contains at least one chromosomal rearrangement and 600 ± 13,000 base substitutions. Intriguingly, tThe spectra and correlation of base substitutions with epigenomic features resemble many cancers.
Moreover, because biopsies were taken from body parts differing by sun exposure (sun-exposed skin cells vs highly protected hip skin cells), authors could delineate precise contributions of environmental vs endogenous factors to the accrual of genetic changes within the same individual..!! They show in this article that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts.
PLoS Genet Oct 2o16; 12(10): e1006385