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Gene mutation combo linked to common cancer in women

August 07, 2019

EAST LANSING, Mich. - Michigan State University researchers, in collaboration with the Van Andel Institute, have identified a combination of two gene mutations that is linked to endometrial cancer.

"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.

The research, published in Nature Communications, found that mutations of the ARID1A and PIK3CA genes are frequently found together in the development of endometrial cancer, as well as in endometriosis-associated ovarian cancer. The findings could mean that better, more targeted treatments can be developed to help fight the disease.

ARID1A is a tumor suppressor. When it mutates, chromatin, cellular material that keeps DNA compacted in cells, loses its structure, allowing cancer to spread. PIK3CA is an instructional gene that tells the body to produce certain proteins and leads to uncontrolled growth of cells when it mutates.

Similarly, these same mutations often are found in women who have endometriosis - a painful condition in which uterine tissue grows outside the uterus - but many of those affected never 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 commonly occurs in women after menopause, suggesting that other factors, such as hormonal changes, environmental exposures or obesity, could combine with the mutations to trigger cancer.

"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."

Through a collaborative effort, Chandler's team provided genetic material to Van Andel Institute. VAI researchers then analyzed the samples with a next-generation sequencer, a machine that rapidly sequences the human genome. This helped MSU researchers identify which gene mutations were associated with the cancer.

"Ten years ago, this research would not have been possible," said Marie Adams, VAI's genomics core manager and a study co-author. "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."
-end-
Other MSU researchers on the study included Mike Wilson, American Cancer Society post-doctoral fellow; Jake Reske, graduate research assistant; Jose Teixeira, professor of obstetrics, gynecology and reproductive biology; Richard Leach, chair of obstetrics, gynecology and reproductive biology department; and Asgerally Fazleabas, associate chair of research and director of women's health research. Hui Shen, associate professor at VAI's Center for Epigenetics, also contributed to the research.

The study was funded by the Mary Kay Foundation and the Ovarian Cancer Research Fund Alliance.

(Note for media: Please include a link to the original paper in online coverage: https://www.nature.com/articles/s41467-019-11403-6)

Michigan State University has been working to advance the common good in uncommon ways for more than 160 years. One of the top research universities in the world, MSU focuses its vast resources on creating solutions to some of the world's most pressing challenges, while providing life-changing opportunities to a diverse and inclusive academic community through more than 200 programs of study in 17 degree-granting colleges.

Michigan State University

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