Powerful genetic sequencing technologies are helping researchers learn more about how changes or errors in genes are linked to disease. Scientists at Michigan State University and the Van Andel Institute have found a combination of mutations in two genes that are linked to endometrial cancer. The findings have been reported in Nature Communications.
"More than 63,000 women are likely to be diagnosed with endometrial cancer this year, making it the most commonly identified type of gynecologic cancer," said Ronald Chandler, an assistant professor of obstetrics, gynecology and reproductive biology in the College of Human Medicine, who led the study.
A gene called ARID1A codes for a protein that is a part of a complex that regulates gene activity. ARID1A is known as a tumor suppression gene and is often mutated in cancer cells. Mutations in ARID1A disrupt the structure of chromatin, the organized complex of DNA as its packaged in the nucleus with associated proteins. Chromatin architecture has to be carefully controlled by the cell, and when that control is lost, cancer is the result.
PIK3CA is one piece of an enzyme and helps the cell control which genes are expressed. It has also frequently been found to be mutated in cancer. Mutations in both ARID1A and PIK3CA are often observed in developing endometrial cancer and endometriosis-associated ovarian cancer.
These genetic mutations are also frequently seen in endometriosis patients. In endometriosis, uterine tissue begins to grow outside of the uterus but still functions as uterine tissue, leading to serious complications and pain. But not everyone with these mutations goes on to develop endometrial cancer.
"We're trying to understand why some women with the same set of mutations get cancer and some don't," Chandler said. "There is something else involved."
Endometrial cancer is more common in post-menopausal women. Hormonal changes or environmental triggers may have an influence. Knowing more about how these mutations are working can help in the creation of better therapeutics or preventive measures.
"The hardest part of our job is figuring out what's causing it," Chandler said. "Is it something in the environment or it is something else? It's a complex process. These are big questions that we're trying to address."
Rapid genomic sequencing technologies have allowed researchers to sequence huge amounts of material in a short period of time, which would have taken years only a few years ago.
"Ten years ago, this research would not have been possible," said study co-author Marie Adams, VAI's genomics core manager. "Next-generation sequencers are powerful new tools we can use to process large-scale projects and provide actionable results in weeks as opposed to years."