News | Tracing Ovarian Cancer: Mayo Clinic Study Identifies a Possible Cell of Origin
Ovarian cancer is called a "silent killer" for good reason: there is currently no effective early screening method, and about 75% of cases are diagnosed at an advanced stage (stage III or IV), often after the cancer has spread elsewhere.
Now, a Mayo Clinic research team may have found clues to ovarian cancer's origins in an unusual 22-year-old patient, offering new possibilities for future screening and prevention.
The patient carried a BRCA2 mutation associated with hereditary breast and ovarian cancer syndrome (HBOC) and a TP53 mutation that causes Li-Fraumeni syndrome. Both are rare genetic abnormalities that substantially increase lifetime cancer risk. When she was diagnosed with breast cancer at Mayo Clinic, imaging also found an ovarian cyst. Although benign, she chose bilateral mastectomy and removal of her ovaries and fallopian tubes (bilateral salpingo-oophorectomy, BSO) to reduce her cancer risk as much as possible.
Precancerous abnormalities appear before a tumor
Further analysis of the removed fallopian tube tissue revealed an unexpected finding: hidden signs of early lesions in epithelial cells that may represent the first step in ovarian cancer development.
"For the first time in this high-risk population, we observed an abnormal developmental trajectory in fallopian tube epithelial cells."
—Dr. Nagarajan Kannan, director of Mayo Clinic's Stem Cells and Cancer Biology Laboratory and study co-author
Using advanced methods including single-cell RNA sequencing, the researchers traced the differentiation of the patient's epithelial cells. Healthy fallopian tubes usually contain two epithelial cell types: ciliated cells that transport the egg and secretory cells that release nourishing fluid. In this patient, secretory cells were overwhelmingly dominant and ciliated cells were severely depleted. More importantly, the secretory cells showed persistent inflammation, which often precedes cancer development.
"This is the first time this imbalance has been observed at cellular resolution in living human fallopian tube tissue. It may represent the seed stage of ovarian cancer."
—Megan Ritting, study co-author and Mayo Clinic PhD candidate in biomedical sciences
Why the fallopian tube? An answer may be emerging
Clinicians have long suspected that most aggressive ovarian cancers actually begin in the fallopian tubes rather than the ovaries. Evidence explaining why and how they begin has been limited. This study fills an important gap and provides a basis for early intervention.
Notably, no progesterone receptors were detected in the patient's fallopian tube cells. Progestin is a major component of oral contraceptives, and previous research suggests oral contraceptives may reduce ovarian cancer risk by about 50%. This finding indicates that conventional risk-reduction approaches may not work for some high-risk patients.
Living fallopian tube biobank tracks cancer development cell by cell
To investigate the origin of ovarian cancer further, the Mayo Clinic team created a biobank of living human fallopian tube cells and tissues from patients at different risk levels. The tissues are also used to build organoid models—miniature fallopian tubes that simulate the full process of malignant transformation.
"We can now model in organoids how these cells progress step by step toward cancer. This will fundamentally change how we understand ovarian cancer."
—Dr. Jamie Bakkum-Gamez, the patient's surgeon and study co-author
The project will further examine how cells with different genetic backgrounds develop precancerous changes. Findings may help refine personalized risk-management recommendations, the timing of preventive surgery, and fertility planning.
News | Tracing Ovarian Cancer: Mayo Clinic Study Identifies a Possible Cell of Origin
News | Tracing Ovarian Cancer: Mayo Clinic Study Identifies a Possible Cell of Origin
Ovarian cancer is called a "silent killer" for good reason: there is currently no effective early screening method, and about 75% of cases are diagnosed at an advanced stage (stage III or IV), often after the cancer has spread elsewhere.
Now, a Mayo Clinic research team may have found clues to ovarian cancer's origins in an unusual 22-year-old patient, offering new possibilities for future screening and prevention.
The patient carried a BRCA2 mutation associated with hereditary breast and ovarian cancer syndrome (HBOC) and a TP53 mutation that causes Li-Fraumeni syndrome. Both are rare genetic abnormalities that substantially increase lifetime cancer risk. When she was diagnosed with breast cancer at Mayo Clinic, imaging also found an ovarian cyst. Although benign, she chose bilateral mastectomy and removal of her ovaries and fallopian tubes (bilateral salpingo-oophorectomy, BSO) to reduce her cancer risk as much as possible.
Precancerous abnormalities appear before a tumor
Further analysis of the removed fallopian tube tissue revealed an unexpected finding: hidden signs of early lesions in epithelial cells that may represent the first step in ovarian cancer development.
"For the first time in this high-risk population, we observed an abnormal developmental trajectory in fallopian tube epithelial cells."
—Dr. Nagarajan Kannan, director of Mayo Clinic's Stem Cells and Cancer Biology Laboratory and study co-author
Using advanced methods including single-cell RNA sequencing, the researchers traced the differentiation of the patient's epithelial cells. Healthy fallopian tubes usually contain two epithelial cell types: ciliated cells that transport the egg and secretory cells that release nourishing fluid. In this patient, secretory cells were overwhelmingly dominant and ciliated cells were severely depleted. More importantly, the secretory cells showed persistent inflammation, which often precedes cancer development.
"This is the first time this imbalance has been observed at cellular resolution in living human fallopian tube tissue. It may represent the seed stage of ovarian cancer."
—Megan Ritting, study co-author and Mayo Clinic PhD candidate in biomedical sciences
Why the fallopian tube? An answer may be emerging
Clinicians have long suspected that most aggressive ovarian cancers actually begin in the fallopian tubes rather than the ovaries. Evidence explaining why and how they begin has been limited. This study fills an important gap and provides a basis for early intervention.
Notably, no progesterone receptors were detected in the patient's fallopian tube cells. Progestin is a major component of oral contraceptives, and previous research suggests oral contraceptives may reduce ovarian cancer risk by about 50%. This finding indicates that conventional risk-reduction approaches may not work for some high-risk patients.
Living fallopian tube biobank tracks cancer development cell by cell
To investigate the origin of ovarian cancer further, the Mayo Clinic team created a biobank of living human fallopian tube cells and tissues from patients at different risk levels. The tissues are also used to build organoid models—miniature fallopian tubes that simulate the full process of malignant transformation.
"We can now model in organoids how these cells progress step by step toward cancer. This will fundamentally change how we understand ovarian cancer."
—Dr. Jamie Bakkum-Gamez, the patient's surgeon and study co-author
The project will further examine how cells with different genetic backgrounds develop precancerous changes. Findings may help refine personalized risk-management recommendations, the timing of preventive surgery, and fertility planning.
Source:
Collected online