Kentsis, A. and Frank, S. A. 2020. Developmental mutators and early onset cancer. Frontiers in Pediatrics 8:189.

A new hypothesis suggests that somatic genome remodeling during normal development can cause mutations that explain many early onset cancers in children and adults.

Currently, only about 10% of early onset cancers can be explained by known inherited cancer predisposition, environmental mutagens or oncogenic pathogens. What explains the majority of cancers of children and young adults? We suggest that developmental mutators may be important. A developmental mutator is a genomic process active during normal tissue development that promotes specific somatic mutations. Enhanced mutations during development lead to tissue-specific somatic mosaicism, because mutations during development propagate to all descendant cells. A mosaic individual who carries a significant fraction of mutated cells has an elevated risk of early onset cancer, especially if the mutation process tends to affect proto-oncogenes or tumor suppressor genes that regulate developmental processes.