Age reshapes evolutionary selection on melanoma driver mutations in 5472 tumors

Researchers analyzed 5472 melanoma samples to determine how patient age influences tumor evolution, publishing their findings in Science Advances. The team evaluated selection intensity on specific genetic variants while correcting for differences in neutral mutation accumulation across age groups science.orgScience Advancesscience.orgOpen source ↗.

Neutral mutation rates increased only modestly as patients aged. Ultraviolet-induced damage remained the primary mutational mechanism across all cohorts, though endogenous mutational processes contributed more substantially to tumors in older individuals.

Evolutionary selection on primary oncogenic drivers varied significantly with age. The selective advantage conferred by the BRAF V600E mutation declined sharply in older tumors, whereas NRAS Q61 mutations gained an evolutionary advantage. TERT promoter mutations occurred more frequently in older cohorts despite exhibiting a lower selective advantage, showing that aging alters melanoma evolution primarily through selective pressure rather than mutation rates.