Discovery of a Novel Gene for Hereditary Colon Cancer

When it comes to strong polyp formation in the large intestine, develops from untreated likely cancer. Often the mass occurrence of polyps is based on a hereditary cause; the disease can be clustered in certain families occur. Under the auspices of human genetics at the University Hospital of Bonn, a research team discovered in patients genetic changes in MSH3 gene and identified so that a new rare form of hereditary colon cancer. The results have now been published in the "American Journal of Human Genetics".

colon cancer
Dr. Ronja Adam, Prof. Dr. Stefan Aretz and Dr. Isabel Spier (from left) of the working group "Familial Colorectal Cancer" at the Institute of Human Genetics at the University Hospital Bonn. Photo: Andreas Stein / Human Genetics

Colon polyps grow as a mushroom-shaped growths of the mucous membrane and be a few millimeters to centimeters. They are benign and cause mostly no complaints – but they can be malignant tumors (cancer) degenerate. If a particularly large polyps in the colon, speaking doctors of “polyposis”. Scientists have discovered several genes that are associated with polyposis.”However, about one third of the area of pathology family has no abnormalities in these genes,” says Prof. Dr. Stefan Aretz, group leader at the Institute of Human Genetics at the University Hospital Bonn. Therefore, there must be more genes that are involved in the formation of polyps in the colon.

Along with pathologist at the University Hospital Bonn, scientists at the Yale University School of Medicine in New Haven (USA) and the University Hospital in Frankfurt, the team led by Prof. Aretz the genotype examined by more than 100 polyposis patients based on blood samples. In each patient, all were known, examined about 20,000 protein-coding genetic simultaneously. The rare, potentially relevant genetic alterations like the proverbial needle in a haystack, the researchers filtered out of the huge amount of data. In two patients, genetic mutations were discovered (mutations) in MSH3 gene on chromosome 5.

Evidence of causes like a circumstantial process

“The challenge is to demonstrate the causal link between the mutations in this gene and the disease,” said Prof. Aretz. The procedure is similar to a circumstantial process. Here, the family members play a role: The diseased siblings have the same MSH3 mutations wear as the first patient being examined, but not the healthy relatives. That was the case. In addition, the scientists, the consequences of the loss of function of MSH3 gene in the patients studied. “It is a gene for the repair of the genetic material,” says Dr. Ronja Adam, one of the two first authors from the team of Prof. Aretz. “The mutations cause the MSH3 protein is not formed.” Since the protein was missing in the nucleus of various tissues, where it caused the accumulation of genetic errors. The unrepaired mutations lead then, among other things to increased incidence of polyps in the colon.The newly discovered polyposis type is unlike many other forms of hereditary colon cancer is not inherited dominant, but recessive. “This means that for siblings, there is a risk of the disease by 25 percent; Parents and children of the persons affected but have a very low risk of the disease, “explains Dr. Isabel Spier from the Institute of Human Genetics, who was also instrumental in the study.

Opportunities for better diagnosis and new drugs

The annual colonoscopy (colonoscopy) is the most effective method of cancer prevention at polyposis patients. In this way, the occurrence of colorectal cancer can be effectively prevented. By studying the MSH3 gene may in future be made in some other, hitherto unexplained cases a clear diagnosis. Healthy persons at risk of families can be tested on the mutations then. “Only proven carriers must then take the intensive screening program to complete,” says the geneticist. Moreover, the science gains by the identification of mutations in the gene MSH3 new insights into the origins and the biological basis of tumors. Prof. Aretz: “The knowledge of the molecular mechanisms that lead to cancer, is also a prerequisite for the development of new drugs.” Publication: Exome sequencing Identifies biallelic MSH3 germline mutations as recessive subtype of colorectal adenomatous polyposis, The American Journal of Human Genetics, DOI: 10.1016 / j.ajhg.2016.06.015 media Contact: Prof. Dr. Stefan Aretz Institute of Human Genetics Biomedicine University of Bonn Tel. 0228/28751009Email: