Related Experiment Video
Updated: Mar 27, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Gorlin syndrome with an ovarian leiomyoma associated with a PTCH1 second hit
Yoshika Akizawa1,2, Toshiyuki Miyashita3, Ryo Sasaki4
1Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan.
Abstract:
We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS.
Insights
Gorlin syndrome (GS) involves PTCH1 mutations. This case reveals distinct second hit mutations in both keratocystic odontogenic tumors and an ovarian tumor, offering new insights into GS tumor development.
Area of Science:
- Genetics
- Oncology
- Dermatology
Background:
- Gorlin syndrome (GS) is a rare autosomal dominant disorder.
- GS is characterized by multiple basal cell nevi, medulloblastomas, skeletal abnormalities, and ovarian fibromas.
- The PTCH1 gene is a major tumor suppressor gene associated with GS.
Observation:
- A 21-year-old Japanese woman with a history of keratocystic odontogenic tumors (KCOTs) was diagnosed with GS.
- Germline PTCH1 mutation c.1427del T was identified.
- A novel PTCH1 mutation (c.264_265insAATA) was found in a maxillary KCOT, representing a second hit.
- An ovarian leiomyoma exhibited loss of heterozygosity in the 9q22.32-9q31.2 region, including PTCH1, as another second hit.
Findings:
- This is the first report of a GS-associated ovarian tumor with a second hit mutation in the PTCH1 region.
- Two distinct second hit mutations in PTCH1 were identified in different tumors within the same GS patient.
- The findings suggest a role for PTCH1 second hit mutations in the pathogenesis of ovarian tumors in GS.
Implications:
- Understanding the role of second hit mutations in ovarian tumors in GS is crucial.
- Further studies with more cases are needed to clarify the significance of these mutations.
- This research may lead to improved diagnostic and therapeutic strategies for Gorlin syndrome patients.
More Related Videos
09:08Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
09:37Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes