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Updated: Aug 16, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Chromosomal aberrations in cell lines derived from thyroid tumors spontaneously developed in TRbetaPV/PV mice
Drazen B Zimonjic1, Yasuhito Kato, Hao Ying
1Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, 37 Convent Drive MSC 4262, Building 37/Room 4128C, Bethesda, MD 20892-4262, USA. drazen_zimonjic@nih.gov
Abstract:
The etiology and genetic alterations of follicular thyroid carcinoma are not well understood. By targeting a mutation (PV) into the thyroid hormone receptor beta gene (TRbetaPV mouse), we created a knock-in mutant TRbeta(PV/PV) mouse that spontaneously develop follicular thyroid carcinoma with progression to metastasis similar to human follicular thyroid carcinoma. This mouse model provides a valuable tool to ascertain the nature and the extent of genomic rearrangements that occur during carcinogenesis of the thyroid. Spectral karyotyping analysis (SKY) of seven cell lines derived from thyroid tumors developed in TRbeta(PV/PV) mice showed that all of them had abnormal karyotypes, with chromosome number ranging from near-diploid (39-42 chromosomes) to hypotetraploid (63-79 chromosomes). These seven cell lines also exhibited a variety of structural chromosomal aberrations, including common recurrent translocations and deletions. This SKY analysis shows that the development and progression of follicular thyroid carcinoma in knock-in TRbeta(PV/PV) mutant mice comprise recurrent structural and numerical genomic changes, some of which mimic those described in human thyroid cancer.
Insights
A new mouse model with a thyroid hormone receptor beta mutation spontaneously develops follicular thyroid carcinoma. Genomic analysis reveals chromosomal changes similar to human thyroid cancer, aiding research into this disease.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- The genetic basis of follicular thyroid carcinoma (FTC) remains largely unknown.
- Understanding the genomic alterations in FTC is crucial for developing effective treatments.
Purpose of the Study:
- To establish a novel mouse model for studying follicular thyroid carcinoma (FTC) development and progression.
- To investigate the genomic landscape of tumors in a genetically engineered mouse model of FTC.
Main Methods:
- Creation of a knock-in mouse model with a specific mutation (PV) in the thyroid hormone receptor beta gene (TRbetaPV/PV).
- Spectral Karyotyping (SKY) analysis of seven cell lines derived from spontaneous thyroid tumors in TRbetaPV/PV mice.
Main Results:
- TRbetaPV/PV mice spontaneously developed follicular thyroid carcinoma with metastatic potential, mimicking human FTC.
- All analyzed cell lines exhibited abnormal karyotypes, ranging from near-diploid to hypotetraploid.
- Recurrent structural chromosomal aberrations, including translocations and deletions, were identified in the tumor cell lines.
Conclusions:
- The TRbetaPV/PV mouse model is a valuable tool for studying thyroid carcinogenesis.
- Genomic instability, characterized by numerical and structural chromosomal changes, is a hallmark of FTC development in this model.
- These genomic alterations in the mouse model show similarities to those observed in human thyroid cancer, providing insights into disease mechanisms.
