Related Experiment Video
Updated: May 21, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Genetic mutations and prognostic indicators in differentiated thyroid cancer: a molecular perspective
Halim Özçevik1, Müge Öner Tamam2, Gündüzalp Buğrahan Babacan2
1Department of Nuclear Medicine, Hamidiye Medical Faculty, University of Health Sciences, İstanbul, Turkiye.
Background/Aim:
The aim of this study was to investigate the relationship between the presence of the BRAF, HRAS, NRAS, and KRAS gene mutations and the development of dedifferentiation (iodine-refractory disease) and extrathyroidal disease in patients with differentiated thyroid carcinoma (DTC).
Materials And Methods:
The patient group included 77 adults classified as intermediate or high-risk according to the American Thyroid Association's 2015 guidelines who underwent total thyroidectomy followed by radioiodine I-131 (RAI) therapy between June 2014 and December 2022. Clinical data were collected via the hospital information system, including the number of surgeries and RAI treatments and the levels of thyroglobulin (Tg), anti-thyroglobulin, and thyroid-stimulating hormone. The histopathological subtypes of DTC were reevaluated, and mutation analyses of the BRAF, KRAS, NRAS, and HRAS genes were performed using real-time polymerase chain reaction (PCR). Statistical analyses were conducted using Medcalc software, with p < 0.05 considered significant.
Results:
Of the 77 patients, most had classical papillary thyroid carcinoma, while others represented various subtypes. No mutations were found in BRAF K601E/V600_K601, KRAS G12x-G13D, or NRAS G12-G13; however, NRAS Q61x was found in one patient, HRAS Q61x in 12, and BRAFV600E/Ec in 36. A significant relationship was observed between HRAS Q61x mutation and disease response, alongside a significant association between gene mutations and iodine-refractory disease development (p = 0.0004). A ROC curve analysis indicated a 49.2 ng/mL threshold for Tg with 75% sensitivity and 94.1% specificity.
Conclusion:
The findings suggest that the HRAS Q61x gene mutation is significantly associated with iodine-resistant disease. It may serve as a prognostic biomarker in early-stage thyroid cancer and aid in disease monitoring in metastatic patients.
Insights
The HRAS Q61x gene mutation is linked to iodine-resistant differentiated thyroid carcinoma. This finding may help identify prognostic biomarkers for thyroid cancer patients.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- Differentiated thyroid carcinoma (DTC) can develop into iodine-refractory disease.
- Investigating gene mutations in DTC is crucial for understanding disease progression.
Purpose of the Study:
- To explore the association between BRAF, HRAS, NRAS, and KRAS gene mutations and dedifferentiation in DTC.
- To determine the role of these mutations in extrathyroidal extension of DTC.
Main Methods:
- Retrospective analysis of 77 intermediate/high-risk DTC patients treated between 2014-2022.
- Real-time PCR for mutation analysis of BRAF, KRAS, NRAS, and HRAS genes.
- Clinical and histopathological data were correlated with mutation status.
Main Results:
- HRAS Q61x mutation was significantly associated with iodine-refractory disease (p=0.0004).
- BRAFV600E/Ec mutations were found in 36 patients, HRAS Q61x in 12, and NRAS Q61x in one.
- Thyroglobulin levels showed a threshold of 49.2 ng/mL for disease detection.
Conclusions:
- HRAS Q61x mutation is a significant predictor of iodine-resistant DTC.
- This mutation may serve as a prognostic biomarker for early-stage thyroid cancer.
- HRAS Q61x status could aid in monitoring metastatic DTC patients.
Related Concept Videos
01:33Cancer-Critical Genes I: Proto-oncogenes
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...
01:25Mutagenicity and Carcinogenicity
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...
02:07Tumor 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...
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...