The causes underlying the development of certain types of common cancers have not yet been elucidated. In order to better determine the origin and the sequence of events responsible for the onset of colon cancer, the teams led by Thanos Halazonetis and Stylianos Antonarakis, professors at the University of Geneva (UNIGE), Switzerland, have sequenced the DNA of biopsied tissue from colon polyps.
The results show that these precancerous lesions have a specific profile called 'mutator', which is associated with an increased frequency of acquisition of certain mutations. The study, published December 1, 2012 in the journal Cancer Research, also designates mutations in three specific genes as being the likely initiators of the progression towards malignancy.
At each cell division, the entirety of our DNA, that is some 6.4 billion base pairs, must be replicated. The enzymes engaged in this task work at a prodigious rate of about 1000 base pairs per minute. This sometimes leads to errors, which are usually corrected by other enzymes. However, the repair mechanisms do not work when there is a defect in the DNA replication process, which is the case for cancer cells.
The genome of human cancer cells is generally unstable. The different forms and causes of this characteristic, which results in a greater susceptibility to acquire mutations, are not all known. "In order to explore the genesis and better understand the sequence of events leading to tumor development, we probed the DNA of precancerous lesions," explains Thanos Halazonetis, Professor at the Departments of Molecular Biology and Biochemistry of the UNIGE's Faculty of Science. To do this, the team led by the professor sequenced the exome, which is the part of DNA that codes for proteins, from colon polyps sampled from patients. The researchers were thus able to pinpoint mutations in three specific genes, constituting the likely initial cause on the road to malignancy. "These genes, named APC, CTNNB1 and BRAF, all have a vital role in the cell. In particular, they are involved in cell division and adhesion to other cells, as well as various intracellular signaling pathways," explains Sergey Nikolaev, at the Department of Genetic Medicine and Development of the Faculty of Medecine, and first author of the article.
The researchers also compared the DNA of polyps, which most were precancerous, to that of healthy colon tissue. They discovered in the former an abnormally high frequency of mutations called SNS, characterized by the substitution of a single DNA base by another. "These precancerous lesions have a profile called 'mutator' which is associated with an increase in the frequency of acquiring SNS type mutations. During early development of the polyp, the mutation rate in these cells is normal, and then it accelerates over time," says Thanos Halazonetis.
The mutation rate observed in polyps was sometimes 200 times greater than that present in normal cells, which greatly increases their progression towards a cancerous stage. According to the professor, these polyps become cancerous in five to ten years. Thanks to these findings, recommendations for routine biopsies, usually conducted every five years, could henceforth be refined on a case to case basis.
Thanos Halazonetis | Source: EurekAlert!
Further information: www.unige.ch
More articles from Health and Medicine:
Human Stem Cells Predict Efficacy of Alzheimer Drugs
06.12.2013 | Rheinische Friedrich-Wilhelms-Universität Bonn
Recurring memory traces boost long-lasting memories
05.12.2013 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
International team of scientists develops new feedback method for optimizing the laser pulse shapes used in the control of chemical reactions
In many ways, traditional chemical synthesis is similar to cooking. To alter the final product, you can change the ingredients or their ratio, change the method of mixing ingredients, or change the temperature or pressure of the environment of the ingredients.
Like an accomplished chef, chemists have become very skilled ...
A genetic defect protects mice from infection with influenza viruses
A new study published in the scientific journal PLOS Pathogens points out that mice lacking a protein called Tmprss2 are no longer affected by certain flu viruses.
The discovery was made by researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig in collaboration with colleagues from Göttingen and ...
The Light: Global study gets underway with online user survey
Light has a fundamental impact on our sense of well-being and performance. In cooperation with Zumtobel, a supplier of lighting solutions, Fraunhofer IAO has launched a global user survey of lighting quality in offices. The objective is to identify the best lighting conditions for a variety of spaces and lighting ...
Quantum entanglement, a perplexing phenomenon of quantum mechanics that Albert Einstein once referred to as “spooky action at a distance,” could be even spookier than Einstein perceived.
Physicists at the University of Washington and Stony Brook University in New York believe the phenomenon might be intrinsically linked with wormholes, hypothetical features of space-time that in popular science fiction can provide a much-faster-than-light shortcut from one part of the universe to another.
But here’s the catch: One couldn’t actually ...
A star is formed when a large cloud of gas and dust condenses and eventually becomes so dense that it collapses into a ball of gas, where the pressure heats the matter, creating a glowing gas ball – a star is born.
New research from the Niels Bohr Institute, among others, shows that a young, newly formed star in the Milky Way had such an explosive growth, that it was initially about 100 times brighter than it is now. The results are published in the scientific journal, Astrophysical Journal Letters.
The young ...
06.12.2013 | Materials Sciences
06.12.2013 | Life Sciences
06.12.2013 | Life Sciences
05.12.2013 | Event News
04.12.2013 | Event News
12.11.2013 | Event News