Epigenetic modification and BRAF gene mutation in thyroid carcinoma

Huang, Guo Cai; Chen, Juan; Zhou, Jun; Xiao, Shuai; Zeng, Weihong; Xia, Jiliang; Zeng, Xi

doi:10.1186/s12935-021-02405-w

Cited by 20 publications

(19 citation statements)

References 129 publications

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“…There are a few studies showing differences in methylation and/or gene expression in relation to BRAF mutation. In PTC, 38% of cases exhibit a complete lack of SMOC2 expression, which is attributed to the presence of BRAF V600E mutations [ 74 ]. The results of the analysis of DNA methylation chip indicate that the SMOC2 gene initiator region contains a high-methylation CpG site [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…In PTC, 38% of cases exhibit a complete lack of SMOC2 expression, which is attributed to the presence of BRAF V600E mutations [ 74 ]. The results of the analysis of DNA methylation chip indicate that the SMOC2 gene initiator region contains a high-methylation CpG site [ 74 ]. A significant association was observed between thyroid stimulating hormone receptor ( TSHR ) gene methylation and positive BRAF V600E mutation cases in thyroid cancer [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

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Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

et al. 2023

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The BRAF V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same patients, on a genome-wide scale we tried to identify (a) any association between BRAF mutation and DNA promoter methylation, and (b) if the molecular findings may provide a basis for therapeutic intervention. We included 40 patients with TC (female = 28, male = 12) without distant metastasis. BRAF mutation was present in 18 cases. We identified groups of differentially methylated loci (DML) that are found in (a) both BRAF mutant and wild type, (b) only in BRAF mutant tumors, and (c) only in BRAF wild type. BRAF mutation-specific promoter loci were more frequently hypomethylated, whereas BRAF wild-type-specific loci were more frequently hypermethylated. Common DML were enriched in cancer-related pathways, including the mismatch repair pathway and Wnt-signaling pathway. Wild-type-specific DML were enriched in RAS signaling. Methylation status of checkpoint signaling genes, as well as the T-cell inflamed genes, indicated an opportunity for the potential use of PDL1 inhibitors in BRAF mutant TC. Our study shows an association between BRAF mutation and methylation in TC that may have biological significance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

et al. 2023

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“…Thyroid cancer is the most common malignancy in the endocrine system with continuously increasing incidence and is predicted to become one of the top five most commonly diagnosed cancers by 2030 [ 1 ]. The genetic alteration of BRAF V600E is most commonly observed in thyroid cancer, in particular papillary thyroid carcinoma (PTC), and is associated with the disease displaying an aggressive process [ 2 , 3 , 4 , 5 , 6 , 7 ]. In addition to the BRAF mutation, poorly differentiated (PDTCs) and anaplastic thyroid cancers (ATCs) often have other genetic and/or non-genetic alterations that can lead to the activation of certain signaling pathways involved in cancer cell growth and tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Targeting Tumor Microenvironment Akt Signaling Represents a Potential Therapeutic Strategy for Aggressive Thyroid Cancer

Mirshahidi

Yuan

Simental

et al. 2023

IJMS

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Effects of the tumor microenvironment (TME) stromal cells on progression in thyroid cancer are largely unexplored. Elucidating the effects and underlying mechanisms may facilitate the development of targeting therapy for aggressive cases of this disease. In this study, we investigated the impact of TME stromal cells on cancer stem-like cells (CSCs) in patient-relevant contexts where applying in vitro assays and xenograft models uncovered contributions of TME stromal cells to thyroid cancer progression. We found that TME stromal cells can enhance CSC self-renewal and invasiveness mainly via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. The disruption of Akt signaling could diminish the impact of TME stromal cells on CSC aggressiveness in vitro and reduce CSC tumorigenesis and metastasis in xenografts. Notably, disrupting Akt signaling did not cause detectable alterations in tumor histology and gene expression of major stromal components while it produced therapeutic benefits. In addition, using a clinical cohort, we discovered that papillary thyroid carcinomas with lymph node metastasis are more likely to have elevated Akt signaling compared with the ones without metastasis, suggesting the relevance of Akt-targeting. Overall, our results identify PI3K/Akt pathway-engaged contributions of TME stromal cells to thyroid tumor disease progression, illuminating TME Akt signaling as a therapeutic target in aggressive thyroid cancer.

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“…Many genes and biomarkers related to THCA have been reported. Currently, BRAF mutation, NTRK3 fusion, NRAS mutation, and RET fusion are of concern [ 8 , 9 ]. The discovery of new biomarkers has significantly improved the understanding of the molecular pathogenesis of THCA, thus providing more personalized treatment for patients with THCA.…”

Section: Introductionmentioning

confidence: 99%

TTN mutations predict a poor prognosis in patients with thyroid cancer

et al. 2022

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Objective: We aimed to investigate the relationship between titin (TTN) gene mutations and thyroid cancer (THCA) and to explore the feasibility of the TTN gene as a potential prognostic indicator of THCA. Methods: From TCGA-THCA cohort, we performed a series of analyses to evaluate the prognostic value and potential mechanism of TTN in THCA. These patients were divided into the mutant-type (MUT) group and the wild-type (WT) group. Differentially expressed genes (DEGs) in the two groups were screened using the ‘DESeq2’ R package. Functional enrichment analysis was performed, and the protein–protein interaction (PPI) network, transcription factor (TF)-target interaction networks, and competitive endogenous RNA (ceRNA) regulatory networks were established for the DEGs. The TIMER database was applied for immune cell infiltration. Survival analysis and Cox regression analysis were used to analyze the potential prognostic value of the TTN gene. Results: Differential expression analysis showed that 409 genes were significantly up-regulated and 36 genes were down-regulated. Functional enrichment analysis revealed that TTN gene mutations played a potential role in the development of THCA. Analysis of the immune microenvironment indicated that TTN gene mutations were significantly associated with enrichment of M0 macrophages. Survival analysis showed that the MUT group predicted poorer prognosis than the WT group. Cox regression analysis demonstrated that TTN gene mutations were an independent risk factor for THCA. Nomograms also confirmed the prognostic values of the TTN gene in THCA. Conclusions In summary, our results demonstrated that TTN gene mutations predict poor prognosis in patients with THCA. This is the first study to research TTN gene mutations in THCA and to investigate their prognostic value in THCA.

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Epigenetic modification and BRAF gene mutation in thyroid carcinoma

Cited by 20 publications

References 129 publications

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer

Targeting Tumor Microenvironment Akt Signaling Represents a Potential Therapeutic Strategy for Aggressive Thyroid Cancer

TTN mutations predict a poor prognosis in patients with thyroid cancer

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