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Updated: May 22, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Molecular study of signaling-pathway genes in experimental rat thyroid carcinoma
María Inés Carmona-López1, Manuel De Miguel, Hugo Galera-Ruiz
1Departamento de Citología e Histología Normal y Patológica, Universidad de Sevilla, Sevilla, Spain.
Introduction:
A study was conducted on histological patterns and biomolecular changes in Goitrogen-induced experimental rat thyroid tumors. The link between the histological types observed and N-ras, B-raf, and PI3KCA gene mutations widely reported in human thyroid cancers was explored.
Material And Methods:
An analysis was done on paraffin-embedded tumor tissue sections from Wistar rats receiving 1% potassium perchlorate (KClO(4)) added to the ad libitum drinking-water supply over an 18-month period. Three experimental subgroups were formed, each comprising 10 thyroids: subgroup I (control) consisted of thyroids from untreated controls; subgroups II and III (experimental) consisted of thyroids from KClO(4)-treated rats, displaying capsular, vascular, or both invasion but no metastasis (II), or distant metastasis (III). DNA was extracted from paraffin-embedded tissues. To test for the genetic mutations most widely reported in human thyroid cancers, exon 1 of the N-ras gene, exons 9 and 20 of the PI3KCA gene, and exon 15 of the B-raf gene were amplified and sequenced.
Results:
All tumors were of the follicular type. None of the 20 experimental rat thyroids displayed the expected gene mutations reported in humans. However, 90% of them contained four new B-raf gene mutations and all were silent and did not cause an amino acid substitution in the protein chain.
Conclusions:
Biomolecular analysis suggested that N-ras, PI3KCA, and B-raf gene mutations may not be involved in thyroid tumor formation using the experimental procedure applied in this study. But the four mutations in B-raf, though without functional repercussions, may be a specific marker for this tumor type.
Insights
Goitrogen-induced rat thyroid tumors did not show common human cancer gene mutations (N-ras, B-raf, PI3KCA). However, four new B-raf mutations were found, potentially marking this specific tumor type.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Investigates histological patterns and biomolecular changes in goitrogen-induced experimental rat thyroid tumors.
- Explores the link between observed histological types and common gene mutations (N-ras, B-raf, PI3KCA) found in human thyroid cancers.
Purpose of the Study:
- To determine if specific gene mutations (N-ras, B-raf, PI3KCA) are involved in the development of experimental rat thyroid tumors.
- To analyze biomolecular changes in relation to histological patterns in goitrogen-induced thyroid tumors.
Main Methods:
- Examined paraffin-embedded thyroid tumor tissue sections from Wistar rats treated with potassium perchlorate (KClO(4)) over 18 months.
- Extracted DNA and sequenced specific gene regions (N-ras exon 1, PI3KCA exons 9 & 20, B-raf exon 15) to identify mutations.
Main Results:
- All induced tumors were of the follicular type.
- No N-ras, B-raf, or PI3KCA mutations typically found in human thyroid cancers were detected in the experimental rat thyroids.
- Ninety percent of experimental tumors harbored four novel B-raf gene mutations, all of which were silent and did not alter the protein sequence.
Conclusions:
- N-ras, PI3KCA, and B-raf gene mutations may not play a role in thyroid tumor formation under the experimental conditions used.
- The identified B-raf mutations, despite lacking functional impact, could serve as a specific marker for this experimental rat thyroid tumor model.
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