Finding Hundreds of Mutations in Healthy Cells Also Caused Great Surprise

A development that will make us question everything we know about cancer genes.

Cancer occurs as a result of the accumulation of mutations in genes. However, much remains unknown about the factors that initially cause these mutations. In October 2018, a study published in Science reported how healthy cells, over their lifetime, undergo mutations and compete with one another, with surprising results . The research shows that we need to question everything we know about cancer genes.

Researchers from the Wellcome Sanger Institute at the University of Cambridge analyzed esophageal tissue samples from people aged between 20 and 75, a total of 9 individuals. These people had no health problems or history of esophageal cancer .

The healthy tissue samples collected underwent whole-genome sequencing to map mutations.

According to the Sequencing Results;

• Surprisingly, in each cell of individuals in their 20s, hundreds of mutations were detected. In older individuals, each cell was found to contain more than 2000 mutations. It was also found that only mutations in certain genes had an effect.
• The researchers focused particularly on mutations in the p53 gene . The P53 gene is mutated in all esophageal cancers. In the study, in 10 percent of healthy cells the p53 gene was found to be mutated. Very few of these cells are thought to lead to cancer development.
• The other important gene is NOTCH1. NOTCH1 is a gene that plays a particularly important role in cell division. By middle age, this gene was found to be mutated in half of the cells.
• The NOTCH1 gene is associated with esophageal cancer. In this study, healthy cells were found to have more NOTCH1 mutations. This suggests that mutations in the NOTCH1 gene may protect against cancer.

What Does This Study Tell Us?

• For years, cancer research had focused on sequencing cancer genomes and on mutations commonly found in patients. Common mutations were thought to be the main triggers of cancer. However, these results showed that NOTCH1, thought to be associated with cancer, was actually more frequently mutated in healthy cells.
• This study may enable new approaches to develop in cancer research. The effects of some cancer-associated genes on cancer development may be reassessed in light of these results.
• The importance of examining healthy cells in cancer research has become clear. The effects of these mutations in healthy cells on aging and other diseases can be investigated more comprehensively.
• This study also offers one explanation for why current tests for cancer early diagnosis in the form of liquid (fluid, blood-based) biopsiesare unsuitable for this purpose.
• We Do Not Recommend Liquid Biopsy for Early Cancer Detection in Healthy Individuals! Why?