Related Experiment Video
Updated: Aug 19, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic
1Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267-0529, USA. Yuri.Nikiforov@uc.edu
Abstract:
Recent molecular studies have provided new insights into thyroid carcinogenesis. In thyroid papillary carcinomas at least three initiating events may occur, which are point mutations in the BRAF and RAS genes and RET/PTC rearrangements. Tumors harboring mutant BRAF and RAS are prone to progression to poorly differentiated and anaplastic carcinoma, but most likely require additional mutations to trigger this process. In thyroid follicular carcinomas, two known initiating events are RAS mutations and PAX8-PPARgamma rearrangements, and RAS predisposes to dedifferentiation of follicular carcinomas. p53 and beta-catenin mutations, found with increasing incidence in poorly differentiated and anaplastic carcinomas but not in well-differentiated tumors, may serve as a direct molecular trigger of tumor dedifferentiation. Additional evidence for progression from a preexisting well-differentiated carcinoma to poorly differentiated and anaplastic carcinoma comes from the studies of loss of heterozygosity and comparative genomic hybridization. Molecular studies, although limited by the lack of uniform histologic criteria for poorly differentiated carcinomas, revealed no genetic mutations or chromosomal abnormalities that are unique for poorly differentiated carcinoma and not present in well-differentiated or anaplastic carcinomas. This suggests that poorly differentiated carcinoma, as a group, represents a distinct step in the evolution from well-differentiated to anaplastic thyroid carcinoma, rather than an entirely separate type of thyroid malignancy.
Insights
Thyroid cancer progression involves specific gene mutations like BRAF, RAS, and RET/PTC. Poorly differentiated thyroid carcinoma represents a key step in advancing from well-differentiated to anaplastic types.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Thyroid carcinogenesis involves complex genetic alterations.
- Understanding molecular drivers is crucial for classifying thyroid tumors.
- Progression from well-differentiated to anaplastic thyroid carcinoma is a significant clinical challenge.
Purpose of the Study:
- To elucidate the molecular events underlying thyroid carcinogenesis.
- To investigate the genetic basis for progression in thyroid tumors.
- To clarify the relationship between well-differentiated, poorly differentiated, and anaplastic thyroid carcinomas.
Main Methods:
- Analysis of molecular alterations including gene mutations (BRAF, RAS, p53, beta-catenin), gene rearrangements (RET/PTC, PAX8-PPARgamma), loss of heterozygosity, and comparative genomic hybridization.
- Correlation of molecular findings with distinct thyroid carcinoma subtypes (papillary, follicular, well-differentiated, poorly differentiated, anaplastic).
Main Results:
- Papillary thyroid carcinomas frequently harbor BRAF mutations, RAS mutations, or RET/PTC rearrangements.
- Follicular thyroid carcinomas are associated with RAS mutations and PAX8-PPARgamma rearrangements.
- Mutations in p53 and beta-catenin are increasingly observed in poorly differentiated and anaplastic carcinomas, suggesting a role in dedifferentiation.
- No unique genetic alterations distinguish poorly differentiated carcinoma from well-differentiated or anaplastic types, indicating a continuum.
Conclusions:
- Thyroid papillary and follicular carcinomas arise from distinct initiating molecular events.
- BRAF and RAS mutations promote tumor progression, while p53 and beta-catenin mutations may trigger dedifferentiation.
- Poorly differentiated thyroid carcinoma represents an intermediate stage in the progression from well-differentiated to anaplastic thyroid carcinoma.
Related Concept Videos
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:24Cellular Adaptation IV: Dysplasia and Metaplasia
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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...
02:21Cancers Originate from Somatic Mutations in a Single Cell
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...