Highly Concordant Key Genetic Alterations in Primary Tumors and Matched Distant Metastases in Differentiated Thyroid Cancer

Sohn, Seo Young; Park, Woong-Yang; Shin, Hyun Tae; Bae, Joon Seol; Ki, Chang Seok; Oh, Young Lyun; Kim, Sun Wook

doi:10.1089/thy.2015.0527

Cited by 38 publications

(42 citation statements)

References 41 publications

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“…Full-text of the remaining 40 studies were further evaluated, and 22 studies with 4,907 patients were ultimately included in this meta-analysis 12–17,22,23,27,30–42. All the 22 studies reported the frequency of TERT promoter mutations,12–17,22,23,27,30–42 18 studies were available for analyzing the clinicopathological features and prognostic significance,14–17,22,23,27,31–33,35–42 15 studies investigated the relationship of TERT promoter and BRAF V600E mutations,13,15,16,22,23,27,33–37,39–42 and six of them evaluated the synergetic effect of both mutations 15,24,25,35,37,41. According to the NOS system, 11 studies were classified as high-quality and the other 11 were mid-range.…”

Section: Resultsmentioning

confidence: 99%

Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis

Su¹,

Jiang²,

Wang³

et al. 2016

OTT

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The clinicopathological and prognostic significance of telomerase reverse transcriptase (TERT) promoter mutations have been widely investigated in thyroid cancer; however, the results are still discrepant. Systematic searches were performed in PubMed, Web of Science, Scopus, Ovid, and the Cochran Library databases for relevant articles prior to April 2016. Mutation rates were synthesized by R statistical software. The odds ratio or standardized mean difference with 95% confidence interval was pooled by Stata. A total of 22 studies with 4,907 cases were included in this meta-analysis. TERT promoter mutations tended to present in aggressive histological types including poorly differentiated thyroid cancer (33.37%), anaplastic thyroid cancer (38.69%), and tall-cell variant papillary thyroid cancer (30.23%). These promoter mutations were likely to exist in older patients and males and were well associated with larger tumor size, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, advanced tumor stage, disease recurrence/persistence, and mortality. In addition, TERT promoter mutations (especially C228T) tended to coexist with BRAFV600E mutation, which indicated more aggressive tumor behavior. Therefore, TERT promoter mutations may be promising biomarkers for early diagnosis, risk stratification, prognostic prediction, and management of thyroid cancer.

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Section: Resultsmentioning

confidence: 99%

Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis

Su¹,

Jiang²,

Wang³

et al. 2016

OTT

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“…Marginal association of coexisting RAS and TERT promoter mutations with poor tumor behaviors was seen in limited FTC cohorts (Muzza et al . 2015; Sohn et al . 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The genetic duet of RAS and TERT promoter mutations was shown to be marginally associated with aggressiveness of FTC in relatively small cohorts (Muzza et al . 2015; Sohn et al . 2016; Song et al .…”

Section: Introductionmentioning

confidence: 99%

A six-genotype genetic prognostic model for papillary thyroid cancer

Shen¹,

Liu²,

Xing³

2017

Endocrine-Related Cancer

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A unique prognostic role of the genetic duet of BRAF V600E and TERT promoter mutation in papillary thyroid cancer (PTC) has been recently established, but the role of RAS mutation in this genetic interplay remains to be established. Using The Cancer Genome Atlas (TCGA) data of patients with PTC from 19 medical centers, we investigated interactions among the three mutations in clinical outcomes of PTC. We found that BRAF and RAS mutations were mutually exclusive but both were associated with TERT promoter mutations, with the genetic duet of BRAF/RAS and TERT mutations occurring in 34/388 (8.76%) patients. BRAF/RAS or TERT mutation each alone had no or minimal effect while coexisting BRAF/RAS and TERT mutations had a robust synergistic effect on poor clinicopatholgoic outcomes of PTC, including disease recurrence and patient mortality. For example, PTC recurrence rate was 52% with coexisting BRAF V600E/RAS and TERT promoter mutations versus 6.9% with no mutation, corresponding to a HR of 8.17 (95% CI 3.09–21.58), which remained significant at 14.71 (95% CI 2.79–77.61) after adjustment for clinicopathologic factors and institution. BRAF/RAS mutation or TERT mutation alone minimally affected Kaplan-Meier patient survival curves while the genetic duet was associated with a sharp curve decline. Thus, by confirming and expanding previous findings in single-institution studies, this multicenter data analysis establishes a six-genotype genetic prognostic model for poor outcomes of PTC with a risk order of genetic duet of BRAF V600E/RAS mutation and TERT mutation >>>> BRAF V600E = TERT mutation alone >RAS mutation alone = wild-type genes.

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“…29,30 Prognosis and staging-based treatment decisions have been extensively studied for the BRAF mutation. Multivariate analysis in some but not all studies [54][55][56][57][58][59][60] have demonstrated that BRAF is an independent predictor of recurrence. However, BRAF mutation does not appear to improve prognosis or direct treatment beyond traditional TNM classifications, and the independent use of BRAF would incorrectly upstage the majority of indolent behaving, lower stage classical PTCs.…”

Section: Thyroseq Ngs Assaymentioning

confidence: 99%

Molecular testing for thyroid nodules: Review and current state

Roth

Witt

Steward

2017

Cancer

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Thyroid nodules affect nearly two-thirds of the world population. Fine-needle biopsy with cytologic evaluation remains the diagnostic test of choice to distinguish benign from malignant thyroid nodules yet fails to discriminate as benign or malignant in up to one-third of cases. This review discusses the limitation of current cytopathologic evaluation, the development of thyroid molecular testing, and the strengths and limitations of commercially available tests. Initial cytomolecular testing sought to identify specific gene mutations associated with thyroid cancer. Although the presence of a mutation was strongly associated with cancer, the likelihood of identifying a mutation was low; therefore, the test had low sensitivity. Subsequent tests developed have sought to improve the accuracy of cytomolecular testing for thyroid fine-needle aspirations, both to reassure patients and providers when malignancy may be absent and to confirm the malignancy when present. The development of cytomolecular testing for thyroid nodules has informed and improved current understanding of thyroid nodule formation and progression. When used appropriately and with clear understanding of the advantages and disadvantages, cytomolecular testing has the potential to improve patient care in the setting of indeterminate thyroid nodules by helping to guide both the need for and the extent of thyroid surgery. Cancer 2018;124:888-98. © 2017 American Cancer Society.

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Highly Concordant Key Genetic Alterations in Primary Tumors and Matched Distant Metastases in Differentiated Thyroid Cancer

Cited by 38 publications

References 41 publications

Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis

Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis

A six-genotype genetic prognostic model for papillary thyroid cancer

Molecular testing for thyroid nodules: Review and current state

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