Somatic Cancer Mutations Accrue Over Years But Not All Become Cancer
Still a mystery why certain somatic mutations become cancerous while others don’t: It’s not merely a numbers game
When researchers found that ”Somatic mutant clones colonize the human esophagus with age” it came as no surprise. In fact, it just made more sense since the mystery of why some mutations become cancerous while others don’t continues. In the abstract of the below-mentioned article, the authors note that while the numbers of mutations increase with age, it doesn’t mean that those mutations occurring with the highest frequency will become cancer.
The research showed that esophageal biopsies from 'normal' people have tens (while in their 20's) to thousands (after age 50) mutations in their genomes! This even includes oncogenes such as NOTCH1 and TP53!
I guess it’s more of a surprise that there isn't more cancer than there is. Our immune system must 'clean up' a lot of early cancers (we've known that immunosuppression does lead to an increase in cancer cases).
Cancer genetics is complicated - you heard it here first!
Abstract The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging. Source: Research article from Science Magazine.