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Home NEWS Science News

Endometrial cancer mutations are detectable in uterine lavage fluid before cancer diagnosis

Bioengineer by Bioengineer
December 30, 2016
in Science News
Reading Time: 4 mins read
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Mutations that have been linked to endometrial cancer can be found in the uterine lavage fluid of pre- and post-menopausal women both with and without detectable cancer, according to a study published in PLOS Medicine by John Martignetti, MD, PhD of the Icahn School of Medicine at Mount Sinai and colleagues.

"Today, there are no effective screening methods for endometrial cancer, which is increasing in both incidence and mortality in the United States," said Peter Dottino, MD, Director of Gynecologic Oncology at Mount Sinai Health System and one of the senior authors on the study. "We were therefore interested in the possibility of coupling newly developed genomic technologies with current treatment practices to develop a precision medicine assay for screening and early detection of this cancer."

In the new study, researchers performed uterine lavage – where the inside of the uterus is rinsed with saline fluid to collect loose cells and cell free DNA – on 107 women undergoing diagnostic hysteroscopy due to post-menopausal uterine bleeding or abnormal pelvic ultrasound results. The collected cells and DNA were analyzed by the research teams, including those of Boris Reva, PhD and Robert Sebra, PhD of the Icahn School of Medicine at Mount Sinai, in collaboration with the advanced research team at Swift Biosciences who together developed sets of targeted gene panels to sequence specific genes known to be associated with endometrial cancer development and progression. In parallel to the genetic study, the hysteroscopy samples were analyzed separately from the advanced genetic workflow using traditional gold-standard classic histopathology methods.

In this prospective study of 107 women, 7 were found to have endometrial cancer based upon histopathological evidence and all 7, even those with only microscopic evidence of cancer, had significant cancer-driver gene mutations detected in their uterine lavage fluid, including both the celluar and cell free DNA. Surprisingly, 51 women with no histopathological evidence of cancer also carried cancer-driver mutations in the cells or the cell free DNA from their lavage fluid. Age and post-menopausal status were both positively associated with the likelihood of harboring these mutations. Due to this unexpected finding, uterine lavage fluid by itself was not able to distinguish between women with and without clinically relevant evidence of endometrial cancer. Additional research is required to understand the significance of driver mutations in women without evidence of cancer to determine whether and how these pre-cancerous mutations can lead to cancer.

"Swift has been at the forefront of cancer research, contributing technologies which redefine the process by which cancer can be detected," said Tim Harkins, PhD, CEO of Swift Biosciences and an author of the publication. "We are proud of the commitment and effort of our collaborative teams to this research, and we are excited that the sensitivity of our genomic technologies has the potential to further the understanding of endometrial cancer in a translational setting. As one might expect, earlier detection of cancer has always improved the outcome of the patient, regardless of the type of cancer. Our goal is to develop technologies that can detect driver mutations in pre-cancerous cells and associated samples, leading to key understandings about how cancer starts and arming us with invaluable information for the ongoing search for a cure."

John M. Murphy, MD, President and CEO of the Western Connecticut Health Network (WCHN) noted that, "Translating the findings from this precision oncology study to earlier cancer detection in women has the potential to transform current clinical care." Dr. Martignetti's research groups at WCHN's newly created Laboratory for Translational Research and the Mount Sinai Health System will work collaboratively to further the state-of-the-art precision medicine program linking gynecologic/oncology patient clinical care and genomic information to improve treatment and surveillance of women with gynecologic cancers.

"Since a uterine lavage can be easily and quickly performed in a physician's office, our initial idea was that this molecular approach could lead to early detection of pre-cancerous and cancerous conditions of the uterus," said John Martignetti, MD, PhD, Associate Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, and Network Director for the Laboratory for Translational Research at WCHN. "However, these findings go beyond genetic screening since they have implications for both molecular diagnostics and raise previously unexplored questions into endometrial cancer development and its possible interruption. The next phase of our ongoing research with 1,000 women enrolled from across multiple institutions will help us to begin sorting out these questions which will ultimately be key to improving upon cancer care."

"By discovering a previously unrecognized cancer gene mutation landscape in women both with and without cancer, this work represents a powerful opportunity to gain new insights into why some women remain healthy and cancer-free while others succumb to this disease," said Eric Schadt, PhD, the Jean C. and James W. Crystal Professor of Genomics at the Icahn School of Medicine at Mount Sinai, and Founding Director of the Icahn Institute for Genomics and Multiscale Biology. "Understanding why some women remain resilient to developing endometrial cancer has implications not only for this cancer but may possibly lead to greater understanding across many cancers."

###

Research Article

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002206

Media Contact

John Martignetti
[email protected]
212-241-9200
@mountsinainyc

http://www.mountsinai.org

############

Story Source: Materials provided by Scienmag

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