Variation in oncogenic protein mutations are greater than previously thought - Finnish research promotes pharmaceutical development
Mutations in proteins make the body vulnerable to the formation of cancer. In most cases, cancer is the result of a series of mutations, not just a single defective gene. However, certain genetic mutations significantly increase the risk of cancer.
KRAS is the gene that controls cell division. When the glycene 12-amino acid mutates, the KRAS protein takes on oncogenic properties. Indeed, the protein in question has been found to be the cause of several different types of cancer.
The research group is now using computer simulations of molecular dynamics to examine the impact that mutations have on the dynamics and function of the KRAS protein. The study is first to find that different mutations in the same location on the KRAS protein affect its function in various ways at the molecular level.
Point mutation of the KRAS protein glycine 12 amino acid can cause glycine to mutate into any of the six possible different amino acids. All of these mutations can make the protein overactive, thus leading to uncontrolled cell growth and the formation of cancerous tissue.
Previously, all six of the mutations occurring in the same location on the KRAS protein were considered to have the same outcomes. However, each the mutations occurring in the KRAS protein seem to affect its function in their own, individual way, thus posing challenges to treatment and pharmaceutical development.
Furthermore, the mutations are not entirely random in nature: some individual mutations occurring in different types of tissue are more common than others.
Glycine 12 mutations in the KRAS protein are often found in cancerous growths in the colon, lungs and pancreas. These mutations have been found to be especially common in the pancreatic ductal adenocarcinoma. According to the Terveysportti website, pancreatic cancer has a very poor prognosis, with a five-year survival rate of 8%, and is the third leading cause of cancer death in Finland.
The research results help to better understand the oncogenic impacts of different mutations, thus making it easier to develop and choose more effective medical treatments in the future.
The study was a joint effort conducted by the University of Eastern Finland, Tampere University of Technology, University of Tübingen (Germany) and University of Helsinki. A CSC supercomputer was used in the study. The article was published in the esteemed PLOS Computational Biology journal.
PLOS Computational Biology journal, Terveysportti and University of Eastern Finland press release: Variation in cancer-causing KRAS mutations greater than thought