Clustered somatic mutations have been a less-studied aspect of cancer development so far. Because clustered mutations make up such a small percentage of all mutations, they have been generally disregarded. However, upon further investigation, a team has discovered that they play a crucial role in the etiology of human cancer. They have found and defined a hitherto unknown critical player in cancer evolution: clusters of mutations in specific genomic areas. The findings on these mutation clusters could be an incredible contribution to Serum Cancer Biomarkers Market. This is because they lead to the progression of around 10% of human tumors, according to the researchers, and can be used to predict patient survival chances.
The study offers insight into one of the mutation types known as clustered somatic mutations. These mutations are induced by internal and external stimuli such as age or UV radiation and are not inherited.
However, the researchers noticed something peculiar about these mutations that needed additional investigation.
Somatic mutations usually occur at random across the genome. However, a deeper examination of some of these mutations revealed that they were occurring in these hotspots.
In this study, the researchers also discovered several factors that produce clustered somatic mutations. Among these factors are tobacco smoking, alcohol intake, UV exposure, and, most importantly, activating a group of antiviral enzymes known as APOBEC3.
In most cases, APOBEC3 enzymes are present within the cells as part of the cell's immune response. Their primary work is to slice up any of the viruses that succeed in entering the cell. However, the researchers suggest in the study that the APOBEC3 enzymes might be responsible for more harm than good in respect to cancer cells.
The researchers discovered that cancer cells have clusters of mutations occurring across individual ecDNA molecules. These are often replete with circular rings of ecDNA (Extrachromosomal DNA) that harbor known cancer driver genes. According to the researchers, these alterations are attributed to the activity of APOBEC3 enzymes.
They believe that APOBEC3 enzymes mistake ecDNA's circular rings for invading viruses and try to limit and chop them up. This, in turn, hastens cancer progression and is likely to lead to drug resistance. Individual ecDNA molecules form clusters of mutations due to the APOBEC3 enzymes' actions. These clustered mutation rings were given the name kyklonas, which is the Greek word for cyclones.
This lays the groundwork for novel therapeutic approaches, such as limiting the activity of APOBEC3 enzymes and/or targeting extrachromosomal DNA for cancer treatment.