<i>BRAF</i> V600E and <i>TERT</i> Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer With Highest Recurrence

Xing, Mingzhao; Liu, Rengyun; Liu, Xiaoli; Murugan, Avaniyapuram Kannan; Zhu, Guangwu; Zeiger, Martha A.; Pai, Sara I.; Bishop, Justin A.

doi:10.1200/jco.2014.55.5094

Cited by 590 publications

(583 citation statements)

References 35 publications

Supporting

Mentioning

516

Contrasting

Unclassified

Order By: Relevance

“…In particular, in our previous study [21] we found that the coexistence of TERT promoter and BRAF mutations correlated more strongly with most important adverse clinicopathological parameters, including thickness, sentinel node metastases, and absence of regression than either mutation alone. Similar results, notably a significant association between the coexistence of TERT promoter and BRAF mutations and worse outcome in terms of disease-free survival, were reported by Xing et al in papillary thyroid carcinoma [36].…”

Section: Discussionsupporting

confidence: 76%

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

Giordano¹,

Macerola²,

Boldrini³

et al. 2015

J Clin Exp Pathol

View full text Add to dashboard Cite

Background: The mutations detected in the promoter of the telomerase reverse transcriptase (TERT) gene, namely C228T and C250T, were first identified in melanoma and subsequently in several cancer models, notably glioma, thyroid cancer and bladder cancer. Recent findings demonstrate that mutation of the TERT promoter may be one of the most common genetic mechanisms contributing to telomerase activation in malignant cells. Mutation of the TERT promoter appears to be an indicator of worse outcome and is correlated with tumor aggressiveness and patient survival; however, to date the only two published studies reported a very low TERT mutation frequency in non-small cell lung cancer (NSCLC). Additionally, the relationship among the presence of these mutations, Tert expression and clinical outcome is unknown.

show abstract

Section: Discussionsupporting

confidence: 76%

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

Giordano¹,

Macerola²,

Boldrini³

et al. 2015

J Clin Exp Pathol

View full text Add to dashboard Cite

show abstract

“…Similarly, in an earlier report on papillary thyroid cancer, patients with tumors that carried both, TERT promoter and BRAF mutations, had worst clinical, pathologic outcomes and increased recurrences. 25 The impact of targeted therapies, using specific genetic alterations in mitogen-activated protein kinase pathway including BRAF mutations, on melanoma survival is well established. 26 We assumed a similar effect on the seven patients in our study that were treated with vemurafenib or dabrafenib.…”

Section: Cancer Genetics and Epigeneticsmentioning

confidence: 99%

TERT promoter mutations in melanoma survival

Nagore

Heidenreich

Rachakonda

et al. 2016

Intl Journal of Cancer

102

View full text Add to dashboard Cite

Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter.Cutaneous melanoma represents one of the most aggressive skin cancers with its propensity to metastasize and intrinsic resistance to treatment. 1 A majority of melanomas remain localized; however, in a proportion of patients, the tumors metastasize to local and distant organs with dismal outcomes.The refractoriness to treatment of patients with metastasized melanoma has been the main cause of the deaths associated with the disease. 2 Despite increased possibilities, with range of treatments including targeted and immunotherapies, of eliciting stable responses in patients with metastatic melanoma, the long-term prospectus in terms of treatment response is confined to disease management. 3 The identification of patients at risk of developing advanced disease at an early stage through use of somatic mutations as molecular biomarkers remains a valid medical issue.The melanoma genome is characterized by one of the highest prevalence of somatic mutations, and the mutational pattern depicts characteristic ultraviolet signature. 4 Besides recurrent mutations in TERT promoter, BRAF/NRAS, CDKN2A, NF1, PTEN and others genes, various sequencing initiatives have identified mutations in a number of other genes including GRIN2A, RAC1, BCL2L12, STK19, FBXW7 and RPS27. [5][6][7][8][9][10][11][12][13][14] The mutations in the promoter of TERT gene, mainly at 2124 (...

show abstract

“…Recently, PDTC and ATC have been shown to harbor BRAF mutations: 33% and 45%, respectively (Landa et al 2016). Thyroid cancers have been shown to be mutated in certain genes of the metabolic and regulatory pathways such as IDH1 (Hemerly et al 2010, Murugan et al 2010 and TERT (Landa et al 2013, Liu et al 2013b, Xing et al 2014, Qasem et al 2015, respectively. Genetic deregulation of these genes results in hyperactivation of MAPK and PI3K/Akt signaling pathways that drive the cell for uncontrolled cell proliferation, growth, survival, invasion and metastasis in thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNAs: emerging players in thyroid cancer pathogenesis

Murugan

Munirajan

Alzahrani

2018

Endocrine-Related Cancer

Self Cite

110

100

View full text Add to dashboard Cite

Thyroid cancer continues to be the most common malignancy of endocrine glands. The incidence of thyroid cancer has risen significantly over the past 4 decades and has emerged as a major health issue. In recent years, significant progress has been achieved in our understanding of the molecular mechanisms of thyroid carcinogenesis, resulting in significant diagnostic, prognostic and therapeutic implications; yet, it has not reached a satisfactory level. Identifying novel molecular therapeutic targets and molecules for diagnosis and prognosis is expected to advance the overall management of this common malignancy. Long noncoding RNAs (lncRNAs) are implicated in the regulation of various key cellular genes involved in cell differentiation, proliferation, cell cycle, apoptosis, migration and invasion mainly through modulation of gene expression. Recent studies have established that lncRNAs are deregulated in thyroid cancer. In this review, we discuss extensively the tumor-suppressive (for example, LINC00271, MEG3, NAMA, PTCSC1/2/3, etc.) and oncogenic (for example, ANRIL, FAL1, H19, PVT1, etc.) roles of various lncRNAs and their possible disease associations implicated in thyroid carcinogenesis. We briefly summarize the strategies and mechanisms of lncRNA-targeting agents. We also describe the potential role of lncRNAs as prospective novel therapeutic targets, and diagnostic and prognostic markers in thyroid cancer.

show abstract

BRAF V600E and TERT Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer With Highest Recurrence

Cited by 590 publications

References 35 publications

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

TERT promoter mutations in melanoma survival

Long noncoding RNAs: emerging players in thyroid cancer pathogenesis

Contact Info

Product

Resources

About