If you thought your cell were mostly normal, it might be time to guess again. Your body may in fact be a shrine to colonies of mutant clones. It’s common knowledge that mutations in cells are what give rise to cancer, but far less is known about what gives rise to mutations in the first place. Now, scientists have discovered even healthy people’s tissue can be “riddled” with genetic mutations, to the extent researchers describe as shocking. “We discovered that by the time an individual reaches middle age, they probably have more mutant than normal cells,” says oncologist and cancer researcher Phil Jones from the Wellcome Sanger Institute in the UK. Jones and his team used genome sequencing techniques to map groups of mutant cells in donated oesophageal tissue from nine deceased individuals aged between 20 to 75 years old at the time of their death. Because these individuals had no known history of chronic disease and or oesophageal problems, their tissue was considered healthy for the purposes of the study but as the research team found out, healthy doesn’t mean free from colonisation by mutant clone cells. “Under the microscope, the oesophageal tissue looked completely normal,” says Jones. “After studying the genetics, we were shocked to see that the healthy oesophagus was riddled with mutations.” The research follows up a 2015 study by some of the same team that found healthy eyelid skin cells harboured a high number of somatic mutations – the kind we get through cell division as we age, and which aren’t passed down to offspring. The study found that 25 percent of skin cells analysed carried at least one of these somatic mutations linked to cancer. To see whether the same prevalence of mutations occurred deeper inside the body, the researchers examined oesophageal tissue; while the latest study is only based on samples from nine donors, the findings suggest these mutant cells pile up rapidly as we get older. In their twenties, people may carry several hundred mutations per cell in healthy oesophageal tissue, but by the time they’re decades older, their still healthy and otherwise normal-functioning tissue could carry over 2,000 mutations per cell. There’s no suggestion that all of these mutations are necessarily malignant, but their mere abundance suggests our understanding of how cancers develop could be due for a rethink, especially since some of the mutations have previously been linked with tumours. In particular, a mutated gene called TP53 (implicated in most oesophageal carcinomas) was found to be mutated in up to 37 percent of healthy cells. More puzzlingly, a gene called NOTCH1 (which helps control cell division) was found to be mutated in up to 80 percent of the healthy cells a prevalence of mutation even higher than in oesophageal cancers. Hypothetically, that mismatch could mean some mutations may even confer a benefit to health in terms of ageing and disease potentially protecting cells from tumours in what the researchers describe as a “hidden world of somatic mutation and clonal competition” in healthy tissue. It’s early days, but the findings could give us a new biological landscape to study how our own cells “mutate, compete, and evolve to colonise our tissues as we age”, explains joint lead author of the study, Inigo Martincorena. “Given the importance of these mutations to cancer, it is remarkable that we have been unaware of the extent of this phenomenon until now.” The findings are reported in Science.
Science Alert, 22 October 2018 ; http://www.sciencealert.com.au