Related Experiment Video
Updated: Jul 28, 2025
05:39
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
1.7K
Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic
Athanasios Bikas1,2, Sara Ahmadi1,2, Theodora Pappa1,2,3
1Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Summary
RAS mutations in thyroid cancer indicate a worse prognosis when additional genetic alterations are present. Genomic profiling helps determine aggressive phenotypes and informs clinical decisions for better patient outcomes.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- RAS mutations are prevalent in various thyroid neoplasms, necessitating improved prognostic tools.
- Understanding the impact of co-occurring genetic events is crucial for managing RAS-mutant thyroid cancers.
Purpose of the Study:
- To investigate how additional genetic alterations influence prognosis in patients with RAS-mutant thyroid cancers, particularly differentiated thyroid cancer (DTC).
- To correlate the presence of secondary mutations with clinical features and outcomes in thyroid cancer patients.
Main Methods:
- Clinical-genomic analysis of 78 patients with differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), or anaplastic thyroid cancer (ATC) undergoing next-generation sequencing.
- Comparison of clinical features and outcomes between patients with solitary RAS mutations and those with RAS plus additional oncogenic alterations.
Main Results:
- Twenty-two percent (17/78) of patients had RAS mutations with additional oncogenic alterations; all anaplastic thyroid cancers (ATCs) had secondary mutations.
- Patients with DTC and additional mutations showed higher rates of high-risk recurrence (77% vs. 12%), larger tumors (4.7 vs. 2.5 cm), and advanced stage disease (67% vs. 3%).
- DTC-specific mortality was over 10-fold higher in patients with additional mutations compared to those with solitary RAS mutations (20% vs. 1.8%).
Conclusions:
- Additional genetic mutations in RAS-mutant thyroid cancers are associated with a more aggressive phenotype and increased mortality risk in DTC.
- Genomic profiling of differentiated thyroid cancers can identify patients at higher risk, guiding clinical decision-making.
- These findings help explain the variable clinical behavior observed in RAS-mutated thyroid neoplasms.
Related Concept Videos
02:38The Ras Gene
6.3K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.3K
01:33Cancer-Critical Genes I: Proto-oncogenes
9.0K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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...
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...
9.0K
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
01:24Small GTPases - Ras and Rho
4.0K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.0K
01:20The Retinoblastoma Gene
4.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K