Researchers find genetic changes in the MSH3 gene in patients with hereditary colon cancer -
The formation of a large number of polyps in the colon a high probability of developing colon cancer if left untreated. The emergence of large-scale polyps is often due to a hereditary cause; in this case, the disease can occur in multiple members of the family. Under the direction of human geneticists from the Bonn University Hospital, a team of researchers has discovered genetic changes in gene MSH3 patients and identified a new rare form of hereditary colon cancer. The results were published in "The American Journal of Human Genetics".
Colon polyps formed as mushroom-shaped protrusions of the mucosa and of several millimeters to several centimeters in size. They are mild and usually cause no symptoms - however, they can turn into malignant tumors (colon cancer). Doctors refer to the development of a large number of polyps in the colon as "polyps". Scientists have discovered several genes associated with polyposis. "However, about a third of families affected by the disease do not have abnormalities in these genes," says Prof. Dr. Stefan Aretz, Head of the working group at the Institute of Human Genetics at the University Hospital of Bonn . therefore, it could still take more genes involved in the formation of polyps in the colon.
Together with the pathologists of the university hospital of Bonn, scientists from Yale university School of Medicine in New Haven (USA) and the university hospital in Frankfurt, the team working with Professor Aretz investigated the genetic material (DNA) of more than 100 patients with polyposis using blood samples. in each patient, the all genes of about 20,000 coding for known proteins were examined simultaneously. in this process, scientists filtered rare genetic changes, possibly relevant to the huge amount of data, like a needle in a haystack. In two patients, the genetic changes (mutations) were found in the MSH3 gene on chromosome 5.
The evidence of the causes is like a trial based on circumstantial evidence
"The challenge proves the causal link between mutations in this gene and the disease, "says Professor Aretz. The process is similar to that of a trial based on circumstantial evidence. Family members also play a role here: The brothers and sisters with the disease should have these same mutations MSH3 the patient was first examined, but not healthy parents. This was the case. In addition, scientists have studied the consequences for patients due to loss of function of the gene MSH3. "This involves a gene to repair the genetic material," says Dr. Ronja Adam, one of the two main authors of the Professor Aretz team. "The mutations cause protein MSH3 not be formed." Given that the protein is not present in the cell nucleus of the patient's tissue, there is an accumulation of genetic defects. the mutations are not repaired then predispose to more frequent occurrence of polyps in the colon.
the type newly discovered polyposis, unlike many other forms of hereditary colon cancer, hereditary non-dominant, but recessive. "This means that the siblings have a chance of developing the disease 25 percent, but parents and children affected people only have a very low risk of developing the disease, "says Dr. Isabel Spier of the Institute of human genetics, which was also very involved in the study.
Opportunities for better diagnostics and new drugs
annual colonoscopy is the most effective cancer screening method for patients with polyposis. Therefore, the development of colon cancer can be effectively prevented. By studying the gene MSH3, a clear diagnosis can be made prospectively in some others cases of polyposis previously unexplained. Then the healthy people at risk in the family can be tested for mutations. "Only proven Carriers should take part in the intensive monitoring program," says human geneticist. In addition, science gain new perspectives on development and biological foundations of tumors through the identification of mutations in the gene MSH3. Prof . Aretz ". The knowledge on the molecular mechanisms that lead to cancer is also a prerequisite for the development of new targeted drugs "
EmoticonEmoticon