The researchers used a technology called exome capture massively parallel sequencing (exome sequencing), which shows the exact order of the nucleotides (the four building blocks of DNA) in all of the protein coding genes in the human genome. The ability of this technology to analyze the DNA of all of the genes in the genome in a single experiment, according to Tavtigian, makes it an amazingly powerful tool for genetic research. "We focused on the genes involved in a particular type of DNA repair, because most known breast cancer genes have been found there. That focused analysis allowed us to identify XRCC2 as a breast cancer susceptibility gene in individuals with a family history of breast cancer," says Tavtigian. "From the exome sequencing data, we found two different types of XRCC2 mutations that occur in breast cancer patients."
He explains that one type of mutation causes the gene to create an incomplete version of the protein. The resulting protein is usually dysfunctional. The other type occurs when a single amino acid in the protein is changed.
"It's a subtle change to the protein, but the resulting change in function could range anywhere from innocuous to even worse dysfunction than the incomplete protein causes," says Tavtigian. "Our sequence analyses suggest that we may have found the full spectrum of results in our study."
Further research is underway. "A worldwide effort has already been launched to figure out what fraction of breast cancer is due to mutations in this gene and how high the risk conferred by these mutations actually is," he says.
|Contact: Linda Aagard|
University of Utah Health Sciences