The Damaging Effect of Passenger Mutations on Cancer Progression.

ABSTRACT: Genomic instability and high mutation rates cause cancer to acquire numerous mutations and chromosomal alterations during its somatic evolution; most are termed passengers because they do not confer cancer phenotypes. Evolutionary simulations and cancer genomic studies suggest that mildly deleterious passengers accumulate and can collectively slow cancer progression. Clinical data also suggest an association between passenger load and response to therapeutics, yet no causal link between the effects of passengers and cancer progression has been established. To assess this, we introduced increasing passenger loads into human cell lines and immunocompromised mouse models. We found that passengers dramatically reduced proliferative fitness (∼3% per Mb), slowed tumor growth, and reduced metasta

SUBMITTER: McFarland CD 

PROVIDER: S-EPMC5639691 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature