Related Experiment Videos
Molecular changes in thyroid neoplasia
1Dept of Nuclear Medicine and Endocrine Oncology, Clinic of Oncological Surgery, Maria Skłodowska-Curie Memorial Institute, Gliwice, Poland. bjarzab@io.gliwice.pl
Abstract:
All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.
Insights
Thyroid cancer development differs between papillary and follicular types, with distinct molecular pathways. RET rearrangements are key in papillary cancer, while RAS mutations are crucial for follicular tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Thyroid cancer comprises distinct histotypes with unique molecular underpinnings.
- Understanding these differences is crucial for targeted therapies and prognostication.
Purpose of the Study:
- To delineate the distinct molecular pathways of papillary and follicular thyroid carcinogenesis.
- To investigate the role of specific genetic alterations in thyroid cancer development and progression.
Main Methods:
- Comparative analysis of genetic alterations (RET rearrangements, RAS mutations, P53 mutations, DNA methylation, aneuploidy) in papillary and follicular thyroid cancers.
- Evaluation of tumor suppressor gene (P16, P53) alterations and chromosomal instability markers.
Main Results:
- RET rearrangements are initiating events in papillary thyroid carcinoma, while RAS mutations are critical in follicular adenomas and contribute to papillary cancer progression.
- Aberrant DNA methylation affecting the P16 tumor suppressor gene is common in both types.
- Follicular cancers show higher aneuploidy rates, whereas papillary cancers have lower rates of loss of heterozygosity and microsatellite instability.
- P53 mutations are associated with undifferentiated thyroid cancers and aggressive phenotypes.
- RET/PTC3 mutations were frequently observed in sporadic papillary thyroid carcinoma in Polish children, challenging the hypothesis of RET rearrangements as specific markers for radiation-induced thyroid cancer.
Conclusions:
- Papillary and follicular thyroid cancers follow divergent molecular routes.
- Specific genetic mutations and chromosomal abnormalities characterize each histotype.
- RET rearrangements may not be exclusive markers for radiation-induced pediatric thyroid cancer.