scholarly journals New Insights into the Link between Melanoma and Thyroid Cancer: Role of Nucleocytoplasmic Trafficking

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 367
Author(s):  
Mourad Zerfaoui ◽  
Titilope Modupe Dokunmu ◽  
Eman Ali Toraih ◽  
Bashir M. Rezk ◽  
Zakaria Y. Abd Elmageed ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Malignant Melanoma ◽  
Tumor Suppressor ◽  
Nucleocytoplasmic Transport ◽  
Braf V600e ◽  
Health Concern ◽  
Common Mechanism ◽  
Tumor Aggressiveness ◽  
Nucleocytoplasmic Trafficking ◽  
Tumor Suppressor Proteins

Cancer remains a major public health concern, mainly because of the incompletely understood dynamics of molecular mechanisms for progression and resistance to treatments. The link between melanoma and thyroid cancer (TC) has been noted in numerous patients. Nucleocytoplasmic transport of oncogenes and tumor suppressor proteins is a common mechanism in melanoma and TC that promotes tumorigenesis and tumor aggressiveness. However, this mechanism remains poorly understood. Papillary TC (PTC) patients have a 1.8-fold higher risk for developing cutaneous malignant melanoma than healthy patients. Our group and others showed that patients with melanoma have a 2.15 to 2.3-fold increased risk of being diagnosed with PTC. The BRAF V600E mutation has been reported as a biological marker for aggressiveness and a potential genetic link between malignant melanoma and TC. The main mechanistic factor in the connection between these two cancer types is the alteration of the RAS-RAF-MEK-ERK signaling pathway activation and translocation. The mechanisms of nucleocytoplasmic trafficking associated with RAS, RAF, and Wnt signaling pathways in melanoma and TC are reviewed. In addition, we discuss the roles of tumor suppressor proteins such as p53, p27, forkhead O transcription factors (FOXO), and NF-KB within the nuclear and cytoplasmic cellular compartments and their association with tumor aggressiveness. A meticulous English-language literature analysis was performed using the PubMed Central database. Search parameters included articles published up to 2021 with keyword search terms melanoma and thyroid cancer, BRAF mutation, and nucleocytoplasmic transport in cancer.

A mouse model of BRAF V600E mutated papillary thyroid cancer imitating sporadic conditions

2018 ◽  
Author(s):  
Iva Jakubikova ◽  
Elin Schoultz ◽  
Ellen Johansson ◽  
Shawn Liang ◽  
Konrad Patyra ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mouse Model ◽  
Papillary Thyroid Cancer ◽  
Braf V600e ◽  
Papillary Thyroid

iTSP-PseAAC: Identify Tumor Suppressor Proteins by Using Fully Connected Neural Network and PseAAC

2021 ◽  
Vol 15 ◽  
Author(s):  
Muhammad Awais ◽  
Waqar Hussain ◽  
Nouman Rasool ◽  
Yaser Daanial Khan
Keyword(s):  
Tumor Suppressor ◽  
Cross Validation ◽  
Control Cell ◽  
Normal Function ◽  
In Vivo Studies ◽  
Tumor Suppressor Proteins ◽  
Proposed Model ◽  
Self Consistency

Background: The uncontrolled growth due to accumulation of genetic and epigenetic changes as a result of loss or reduction in the normal function of Tumor Suppressor Genes (TSGs) and Pro-oncogenes is known as cancer. TSGs control cell division and growth by repairing of DNA mistakes during replication and restrict the unwanted proliferation of a cell or activities, those are the part of tumor production. Objectives: This study aims to propose a novel, accurate, user-friendly model to predict tumor suppressor proteins, which would be freely available to experimental molecular biologists to assist them using in vitro and in vivo studies. Methods: The predictor model has used the input feature vector (IFV) calculated from the physicochemical properties of proteins based on FCNN to compute the accuracy, sensitivity, specificity, and MCC. The proposed model was validated against different exhaustive validation techniques i.e. self-consistency and cross-validation. Results: Using self-consistency, the accuracy is 99%, for cross-validation and independent testing has 99.80% and 100% accuracy respectively. The overall accuracy of the proposed model is 99%, sensitivity value 98% and specificity 99% and F1-score was 0.99. Conclusion: It concludes, the proposed model for prediction of the tumor suppressor proteins can predict the tumor suppressor proteins efficiently, but it still has space for improvements in computational ways as the protein sequences may rapidly increase, day by day.

scholarly journals Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

2014 ◽  
Vol 21 (6) ◽  
pp. 891-902 ◽  
Author(s):  
Min-Hee Kim ◽  
Ja Seong Bae ◽  
Dong-Jun Lim ◽  
Hyoungnam Lee ◽  
So Ra Jeon ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Tumour Size ◽  
External Validation ◽  
Allelic Frequency ◽  
The Cancer Genome Atlas ◽  
Braf V600e ◽  
Validation Dataset ◽  
Papillary Thyroid ◽  
Additional Information

The BRAF V600E mutation is the most common genetic alteration in thyroid cancer. However, its clinicopathological significance and clonal mutation frequency remain unclear. To clarify the inconsistent results, we investigated the association between the allelic frequency of BRAF V600E and the clinicopathological features of classic papillary thyroid carcinoma (PTC). Tumour tissues from two independent sets of patients with classic PTC were manually microdissected and analysed for the presence or absence of the BRAF mutation and the mutant allelic frequency using quantitative pyrosequencing. For external validation, the Cancer Genome Atlas (TCGA) data were analysed. The BRAF V600E mutation was found in 264 (82.2%) out of 321 classic PTCs in the training set. The presence of BRAF V600E was only associated with extrathyroidal extension and the absence of thyroiditis. In BRAF V600E-positive tumours, the mutant allelic frequency varied from 8 to 41% of the total BRAF alleles (median, 20%) and directly correlated with tumour size and the number of metastatic lymph nodes. Lymph node metastases were more frequent in PTCs with a high (≥20%) abundance of mutant alleles than in those with a low abundance of mutant alleles (P=0.010). These results were reinforced by validation dataset (n=348) analysis but were not reproduced in the TCGA dataset. In a population with prevalent BRAF mutations, quantitative analysis of the BRAF mutation could provide additional information regarding tumour behaviour, which is not reflected by qualitative analysis. Nonetheless, prospective studies are needed before the mutated allele percentage can be considered as a prognostic factor.

scholarly journals ZIC1 Is a Putative Tumor Suppressor in Thyroid Cancer by Modulating Major Signaling Pathways and Transcription Factor FOXO3a

2014 ◽  
Vol 99 (7) ◽  
pp. E1163-E1172 ◽  
Author(s):  
Wei Qiang ◽  
Yuan Zhao ◽  
Qi Yang ◽  
Wei Liu ◽  
Haixia Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Colony Formation ◽  
Promoter Hypermethylation ◽  
Migration And Invasion ◽  
Thyroid Cancer Cells

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown. Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis. Setting and Design: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes. Methylation-specific PCR was used to analyze promoter methylation of the ZIC1 gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. Results: ZIC1 was frequently down-regulated by promoter hypermethylation in both primary thyroid cancer tissues and thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation was significantly associated with lymph node metastasis in patients with papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest and apoptosis by blocking the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity. Conclusions: Our data demonstrate that ZIC1 is frequently inactivated by promoter hypermethyaltion and functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.

Molecular Diagnostics of Thyroid Tumors

2011 ◽  
Vol 135 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Yuri E. Nikiforov
Keyword(s):  
Thyroid Cancer ◽  
Molecular Markers ◽  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Fine Needle ◽  
Molecular Alterations ◽  
Diagnostic Use

Abstract Context.—Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for diagnosis and prognostication is of high clinical significance. Objective.—To review the most common molecular alterations in thyroid cancer and their diagnostic and prognostic utility. Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author. Conclusions.—The most common molecular alterations in thyroid cancer include BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements. These nonoverlapping genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. These molecular alterations can be detected in surgically resected samples and fine-needle aspiration samples from thyroid nodules and can be of significant diagnostic use. The diagnostic role of BRAF mutations has been studied most extensively, and recent studies also demonstrated a significant diagnostic utility of RAS, RET/PTC, and PAX8/PPARγ mutations, particularly in thyroid fine-needle aspiration samples with indeterminate cytology. In addition to the diagnostic use, BRAF V600E mutation can also be used for tumor prognostication, as this mutation is associated with higher rate of tumor recurrence and tumor-related mortality. The use of these and other emerging molecular markers is expected to improve significantly the accuracy of cancer diagnosis in thyroid nodules and allow more individualized surgical and postsurgical management of patients with thyroid cancer.

Differences of US-FNA BSRTC class, postoperative pathology, and mutation landscape of thyroid nodules between China and other countries.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3055-3055
Author(s):  
Yuntao Song ◽  
Jie Liu ◽  
Weiran Wang ◽  
Tonghui Ma
Keyword(s):  
United States ◽  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Malignant Tumors ◽  
The United States ◽  
Braf V600e ◽  
Class V ◽  
Ras Mutation ◽  
First Choice ◽  
Significant Difference

3055 Background: Ultrasound and ultrasound-guided fine needle aspiration (US-FNA) are the first choice for judging benign and malignant thyroid nodules. This study will report on the differences of US-FNA BSRTC class, postoperative pathology and mutation landscape of thyroid nodules between China and other countries. Methods: We conducted a prospective study containing 383 FNA samples of thyroid nodules. For most of these FNA samples, genomic DNA and RNA were extracted and sequenced with FSZ-Thyroid NGS Panel V1, and postoperative pathology were followed up. Moreover, we also compared results of this study with those of West China Hospital in China, Yamashita Thyroid Hospital in Japan, and Cleveland Clinic in the United States. Results: Among the 383 FNA samples, the proportions of BSRTC class I to VI were 10.7%, 6.3%, 18.8%, 3.7%, 12.3%, and 48.3% respectively. Compared with study in other countries, the proportion of class II was significantly lower than that in Japan and the United States. Meanwhile, the proportion of class V and VI were significantly higher than the above two countries. Subsequently, 232 thyroid nodules were surgically removed. Postoperative pathology showed that the proportion of malignant tumors (85.3%) was also significantly higher than reported in Japan and the United States. But compared with other studies in China, there was no significant difference. Most of the malignant tumors were papillary thyroid cancer (PTC, 96%), accompanied with 2 follicular thyroid cancer (FTC), 3 medullary cancer (MTC) and 3 anaplastic thyroid cancer (ATC). Compared with study in the United States, the proportion of PTC and FTC were elevated (96% vs. 85.3%) and reduced (1% vs. 9.3%) respectively. At last, we also analysis the mutation landscape of 180 malignant tumors. Compared with TCGA study, the frequency of BRAF V600E in PTC in our study was significantly higher than that of TCGA (73.3% vs. 58%), and the frequency of RAS mutation was significantly lower (1.2% vs. 12.6%). And compared with an institutional experience of ThyroSeq v3 for Bethesda III and IV at the University of Pittsburgh Medical Center, the frequency of BRAF V600E and RAS mutation in Bethesda III-IV malignant tumors was also significantly higher (45.8% vs. 1.4%) and lower (8.3% vs. 47.1%). Conclusions: There were significant differences in BSRTC class and postoperative pathology between China and other countries, such as Japan and the United States. The possible reasons included that the indications for FNA in China were different. For example, most of patients who underwent FNA in this study had suspicious clinical/ultrasound features. So the proportion of BSRTC class V and VI as well as the malignant rate were elevated. On the other hand, more BRAF V600E and less RAS mutations were detected in malignant tumors in this study which might result from racial differentiation and discrepancy in proportion of PTC and FTC.

Aberrant Expression of Tumor Suppressor Proteins in the Ewing Family of Tumors

2001 ◽  
Vol 125 (9) ◽  
pp. 1207-1212 ◽  
Author(s):  
Anirban Maitra ◽  
Helen Roberts ◽  
Arthur G. Weinberg ◽  
Joseph Geradts
Keyword(s):  
Tumor Suppressor ◽  
Metastatic Disease ◽  
Malignant Neoplasms ◽  
Down Regulation ◽  
Aberrant Expression ◽  
P16ink4a Expression ◽  
Tumor Suppressor Proteins ◽  
Abnormal Expression ◽  
Ewing Family Of Tumors

Abstract Background.—Deregulation of tumor suppressor gene function and abrogation of cell cycle control are common features of malignant neoplasms, but corresponding data on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We studied the expression of 4 tumor suppressor proteins in the Ewing family of tumors (EFTs). Design.—We examined a series of 20 pediatric EFTs for abnormal expression of p16INK4a, p14ARF, p21WAF1, and pRB by immunohistochemical analysis of pretreatment, nondecalcified archival specimens. Clinical follow up was available in all cases (median, 21 months; range, 5–103 months). Five patients presented with metastatic disease, 8 had no evidence of disease at last follow up, and 12 had an adverse outcome (death or progressive tumor posttherapy). Results.—Twelve cases (60%) demonstrated abnormal expression of at least one tumor suppressor protein. There were 11 cases (55%) with loss of p21WAF1 expression, 4 (20%) with down-regulation of p16INK4a, 2 (10%) with absence of pRB, and one case (5%) with loss of p14ARF expression. Loss of p16INK4a expression correlated with metastatic disease at presentation (P = .026), and showed a trend toward shortened survival (P = .20). The p21WAF1, p14ARF, and pRB status was not significantly correlated with either metastatic disease at presentation or outcome. Conclusion.—Abrogation of the G1 checkpoint was common in this series of EFTs, and down-regulation of p21WAF1 and p16INK4a were the most frequent findings. Loss of p16INK4a expression may identify a subset of cases with a more aggressive phenotype.

Sign in / Sign up

Export Citation Format

Share Document