Related Experiment Video
Updated: Aug 5, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Identifying the Carcinogenic Mechanism of Malignant Struma Ovarii Using Whole-Exome Sequencing and DNA Methylation
Hitomi Yamashita1, Kentaro Nakayama1, Kosuke Kanno1
1Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan.
Background:
Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination.
Methods:
DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed.
Results:
Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis.
Conclusions:
Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.
Insights
Genetic and DNA methylation analysis revealed somatic uniparental disomy and altered methylation in tumor suppressor genes, potentially explaining the carcinogenesis of malignant struma ovarii.
Area of Science:
- Oncology
- Genetics
- Epigenetics
Background:
- Malignant struma ovarii is a rare ovarian tumor.
- The carcinogenic mechanisms are not well understood.
Observation:
- This study investigated a rare case of malignant struma ovarii with peritoneal dissemination.
- Whole-exome sequencing and DNA methylation analysis were performed on tumor and normal tissues.
Findings:
- Germline variants and somatic uniparental disomy (UPD) were identified in tumor suppressor genes RECQL4, CNTNAP2, and PRDM2.
- DNA methylation analysis revealed altered methylation patterns in genes associated with tumor growth suppression, including FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2.
Implications:
- Somatic UPD and DNA methylation in tumor suppressor genes may play a role in the pathogenesis of malignant struma ovarii.
- This study is the first to report whole-exome sequencing and DNA methylation analysis in malignant struma ovarii.
- Genetic and DNA methylation analyses can aid in understanding carcinogenesis mechanisms for rare diseases and inform treatment strategies.
