Little is known about what causes ovarian cancer, and there is no way to detect it early yet. About 75% of the time when someone is diagnosed with ovarian cancer, it has already progressed to stage 3 or stage 4, which means it has spread to other parts of the body.
Mayo Clinic physicians, researchers and patients had been working together to learn more about this devastating disease when a 22-year-old patient, who has two rare genetic conditions that dramatically elevate lifetime cancer risk, came to Mayo Clinic.
The patient carries a hereditary BRCA2 mutation, which is one of the genes that causes hereditary breast and ovarian cancer (HBOC) syndrome, and a hereditary TP53 mutation, which causes Li-Fraumeni syndrome.
At Mayo Clinic, she was diagnosed with breast cancer. Imaging also revealed she had an ovarian cyst. Although the cyst was benign, she chose to have a mastectomy and hysterectomy with removal of her ovaries and fallopian tubes, a procedure called a bilateral salpingo-oophorectomy, because of her elevated cancer risk.
Upon further examination, her Mayo Clinic physician and research team detected early, hidden changes in the cells lining her fallopian tubes, revealing signals that may point to the first signs of ovarian cancer before symptoms or visible lesions appear.
“Our team glimpsed a rare and revealing phenomenon in epithelial biology, uncovered through the cells of a young patient living with profoundly high-risk genetic conditions,” says Nagarajan Kannan, Ph.D., director of the Stem Cell and Cancer Biology Laboratory at Mayo Clinic and co-lead author of this study published in JCO Precision Oncology.
“Using cutting-edge, single-cell technologies, we traced how her epithelial cells were developmentally altered in ways that signaled a high risk for lethal ovarian cancer. These insights could pave the way for future strategies to detect the disease in its earliest, precancerous stages when prevention is still possible.”
Jamie Bakkum-Gamez, M.D., the patient’s gynecologic oncology surgeon at Mayo Clinic, says she is determined to find a way to detect ovarian cancer earlier to help save more patients’ lives.
“We know that the most aggressive and common form of ovarian cancer often actually starts in the fallopian tube. However, why the fallopian tube and how it starts are not yet known. Knowing how ovarian cancer begins and forms could not only lead to the development of earlier screening tools, but also more personalized risk-reduction strategies and improved guidance around the timing of preventive surgeries and fertility planning,” says Dr. Bakkum-Gamez, who is a co-lead author of this study.
Together, Dr. Kannan and Dr. Bakkum-Gamez have established a living fallopian tube biobank at Mayo Clinic. The cells and tissues donated by patients help scientists study how ovarian cancer begins—cell by cell—directly in human tissue.
From the patient specimens, organoids, or small versions of the fallopian tubes, can be grown. The biobank includes organoids from patients with average-to-high ovarian cancer risk and specializes in inherited cancer mutations like the ones associated with HBOC syndrome and Li-Fraumeni syndrome.
“The precise cellular origin of ovarian cancer remains one of the greatest unanswered questions in cancer prevention—limiting our ability to intervene early and save lives. This work lays the foundation for a new era of early detection and precision prevention for ovarian cancer, especially for patients with inherited risk such as BRCA mutations,” says Dr. Kannan.
Ovarian cancer precursor
A healthy fallopian tube consists of two main types of epithelial cells: multiciliated cells that have hundreds of cilia, or hairlike appendages, that help move the fertilized egg through the fallopian tube, and secretory cells that secrete fluids to nourish and protect the developing embryo.
But in the fallopian tube cells collected from the patient with HBOC syndrome and Li-Fraumeni syndrome, the scientists saw something they had never seen before. Instead of the two types of epithelial cells, the secretory cells vastly outnumbered the multiciliated cells across the fallopian tube. They also found that secretory cells were driving chronic inflammation—an established contributor to cancer development.
“Through single-cell RNA sequencing, we could see the disruptions in the development of cells lining the fallopian tube lumen—findings that could help reshape how we understand and ultimately prevent ovarian cancer,” says Megan Ritting, co-lead author and Mayo Clinic Graduate School of Biomedical Sciences doctoral candidate. Ritting spearheaded the use of cutting-edge genomic technology in this study.
Furthermore, oral contraceptives containing progestins, or synthetic analogs of the hormone progesterone that is produced by the ovaries, can be used to reduce ovarian cancer risk by up to 50%.
However, Ritting and the research team were surprised to see that this patient’s fallopian tube cells did not have any progesterone receptor proteins, which suggests oral contraceptives may not have been effective in reducing the patient’s risk for ovarian cancer.
“With the generous partnership of patients who allow their cells to be studied using advanced technologies, including organoid models, we are making critical progress in understanding how these cancers develop.
This work represents an important step toward identifying opportunities to develop preventive strategies, treatments and approaches that could reduce the risk of fallopian tube and ovarian cancers,” says Dr. Bakkum-Gamez.
In the next steps of this research, using the living fallopian tube biobank, the scientists are investigating how and where the earliest origins of ovarian cancer take root.
More information:
Megan L. Ritting et al, Epithelial Abnormalities in the High-Risk Fallopian Tube of a Rare TP53 / BRCA2 Li-Fraumeni Syndrome Patient With Multiple Tumors, JCO Precision Oncology (2025). DOI: 10.1200/PO-24-00589
Citation:
Researchers capture first signs of ovarian cancer risk (2025, June 25)
retrieved 25 June 2025
from https://medicalxpress.com/news/2025-06-capture-ovarian-cancer.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
Little is known about what causes ovarian cancer, and there is no way to detect it early yet. About 75% of the time when someone is diagnosed with ovarian cancer, it has already progressed to stage 3 or stage 4, which means it has spread to other parts of the body.
Mayo Clinic physicians, researchers and patients had been working together to learn more about this devastating disease when a 22-year-old patient, who has two rare genetic conditions that dramatically elevate lifetime cancer risk, came to Mayo Clinic.
The patient carries a hereditary BRCA2 mutation, which is one of the genes that causes hereditary breast and ovarian cancer (HBOC) syndrome, and a hereditary TP53 mutation, which causes Li-Fraumeni syndrome.
At Mayo Clinic, she was diagnosed with breast cancer. Imaging also revealed she had an ovarian cyst. Although the cyst was benign, she chose to have a mastectomy and hysterectomy with removal of her ovaries and fallopian tubes, a procedure called a bilateral salpingo-oophorectomy, because of her elevated cancer risk.
Upon further examination, her Mayo Clinic physician and research team detected early, hidden changes in the cells lining her fallopian tubes, revealing signals that may point to the first signs of ovarian cancer before symptoms or visible lesions appear.
“Our team glimpsed a rare and revealing phenomenon in epithelial biology, uncovered through the cells of a young patient living with profoundly high-risk genetic conditions,” says Nagarajan Kannan, Ph.D., director of the Stem Cell and Cancer Biology Laboratory at Mayo Clinic and co-lead author of this study published in JCO Precision Oncology.
“Using cutting-edge, single-cell technologies, we traced how her epithelial cells were developmentally altered in ways that signaled a high risk for lethal ovarian cancer. These insights could pave the way for future strategies to detect the disease in its earliest, precancerous stages when prevention is still possible.”
Jamie Bakkum-Gamez, M.D., the patient’s gynecologic oncology surgeon at Mayo Clinic, says she is determined to find a way to detect ovarian cancer earlier to help save more patients’ lives.
“We know that the most aggressive and common form of ovarian cancer often actually starts in the fallopian tube. However, why the fallopian tube and how it starts are not yet known. Knowing how ovarian cancer begins and forms could not only lead to the development of earlier screening tools, but also more personalized risk-reduction strategies and improved guidance around the timing of preventive surgeries and fertility planning,” says Dr. Bakkum-Gamez, who is a co-lead author of this study.
Together, Dr. Kannan and Dr. Bakkum-Gamez have established a living fallopian tube biobank at Mayo Clinic. The cells and tissues donated by patients help scientists study how ovarian cancer begins—cell by cell—directly in human tissue.
From the patient specimens, organoids, or small versions of the fallopian tubes, can be grown. The biobank includes organoids from patients with average-to-high ovarian cancer risk and specializes in inherited cancer mutations like the ones associated with HBOC syndrome and Li-Fraumeni syndrome.
“The precise cellular origin of ovarian cancer remains one of the greatest unanswered questions in cancer prevention—limiting our ability to intervene early and save lives. This work lays the foundation for a new era of early detection and precision prevention for ovarian cancer, especially for patients with inherited risk such as BRCA mutations,” says Dr. Kannan.
Ovarian cancer precursor
A healthy fallopian tube consists of two main types of epithelial cells: multiciliated cells that have hundreds of cilia, or hairlike appendages, that help move the fertilized egg through the fallopian tube, and secretory cells that secrete fluids to nourish and protect the developing embryo.
But in the fallopian tube cells collected from the patient with HBOC syndrome and Li-Fraumeni syndrome, the scientists saw something they had never seen before. Instead of the two types of epithelial cells, the secretory cells vastly outnumbered the multiciliated cells across the fallopian tube. They also found that secretory cells were driving chronic inflammation—an established contributor to cancer development.
“Through single-cell RNA sequencing, we could see the disruptions in the development of cells lining the fallopian tube lumen—findings that could help reshape how we understand and ultimately prevent ovarian cancer,” says Megan Ritting, co-lead author and Mayo Clinic Graduate School of Biomedical Sciences doctoral candidate. Ritting spearheaded the use of cutting-edge genomic technology in this study.
Furthermore, oral contraceptives containing progestins, or synthetic analogs of the hormone progesterone that is produced by the ovaries, can be used to reduce ovarian cancer risk by up to 50%.
However, Ritting and the research team were surprised to see that this patient’s fallopian tube cells did not have any progesterone receptor proteins, which suggests oral contraceptives may not have been effective in reducing the patient’s risk for ovarian cancer.
“With the generous partnership of patients who allow their cells to be studied using advanced technologies, including organoid models, we are making critical progress in understanding how these cancers develop.
This work represents an important step toward identifying opportunities to develop preventive strategies, treatments and approaches that could reduce the risk of fallopian tube and ovarian cancers,” says Dr. Bakkum-Gamez.
In the next steps of this research, using the living fallopian tube biobank, the scientists are investigating how and where the earliest origins of ovarian cancer take root.
More information:
Megan L. Ritting et al, Epithelial Abnormalities in the High-Risk Fallopian Tube of a Rare TP53 / BRCA2 Li-Fraumeni Syndrome Patient With Multiple Tumors, JCO Precision Oncology (2025). DOI: 10.1200/PO-24-00589
Citation:
Researchers capture first signs of ovarian cancer risk (2025, June 25)
retrieved 25 June 2025
from https://medicalxpress.com/news/2025-06-capture-ovarian-cancer.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
