Overview

• The Wellcome Sanger Institute refined NanoSeq and, with TwinsUK, analyzed 1,042 cheek swabs and 371 blood samples to map somatic mutations at high resolution.
• Researchers detected more than 340,000 mutations in cheek cells, including over 62,000 in known cancer genes, and identified 49 genes under positive selection.
• Distinct mutational signatures linked to lifestyle were observed, with smokers showing increased NOTCH1 mutations and heavy drinkers displaying a characteristic DNA pattern.
• Most mutated cell clones in normal tissue were very small and did not continue to expand over time, indicating common mutations rarely progress.
• A companion Nature study of 81 sperm samples found disease-causing mutations in about 2% of sperm in men in their early 30s, rising to 3–5% in middle-aged and older men, highlighting a risk that increases with paternal age.