Targeted Next-Generation Sequencing Panel (ThyroSeq) for Detection of Mutations in Thyroid Cancer

Nikiforova, Marina N.; Wald, Abigail I.; Roy, Somak; Durso, Mary Beth; Nikiforov, Yuri E.

doi:10.1210/jc.2013-2292

Cited by 428 publications

(389 citation statements)

References 56 publications

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“…However, these pyrosequencing data are in contrast to the results achieved using NGS and IHC staining. Nikiforova et al (2013) evaluated BRAF mutated alleles using NGS and reported that 80% of PTCs with BRAF V600E had more than 25% of the mutated alleles. In the TCGA dataset, 86% of classic PTCs with BRAF V600E had more than 25% of the mutated alleles.…”

Section: Discussionmentioning

confidence: 99%

Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

Kim¹,

Bae²,

Lim³

et al. 2014

Endocrine-Related Cancer

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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 (R20%) abundance of mutant alleles than in those with a low abundance of mutant alleles (PZ0.010). These results were reinforced by validation dataset (nZ348) 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.

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Section: Discussionmentioning

confidence: 99%

Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

Kim¹,

Bae²,

Lim³

et al. 2014

Endocrine-Related Cancer

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“…36 The performance of this genetic panel was initially evaluated by using thyroid tumors cells and cell lines with known genetic alterations. The ThyroSeq test had a 100% analytic accuracy, as it correctly detected all pathogenic mutations in previously positive thyroid tumor samples and cell lines.…”

Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

“…In addition, all mutations detected by ThyroSeq were confirmed by other molecular testing methods, such as Sanger sequencing, real-time PCR, or coamplification at lower denaturation-PCR, revealing 100% correlation among the different techniques. The initial validation of ThyroSeq panel by Nikiforova et al 36 showed the presence of the tested gene mutations or translocations in various thyroid malignancies, including 19 of 27 classic PTCs (70%), 25 of 30 follicular variant PTCs (83%), 14 of 18 conventional carcinomas (78%), 7 of 18 oncocytic follicular carcinomas (39%), 3 of 10 poorly differentiated carcinomas (30%), 20 of 27 anaplastic thyroid carcinomas (ATCs) (74%), and 11 of 15 medullary thyroid carcinomas (73%). In contrast, only 5 of 83 benign nodules (6%) were positive for mutations.…”

Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Zhang

Lin²

2016

Archives of Pathology &Amp; Laboratory Medicine

100

158

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Context.— Fine-needle aspiration of thyroid nodules is a reliable diagnostic method to determine the nature of thyroid nodules. Nonetheless, indeterminate cytology diagnoses remain a diagnostic challenge. The development of multiplex molecular techniques and the identification of genetic alterations associated with different follicular cell–derived cancers in the thyroid have led to the introduction of several commercially available tests. Objective.— To summarize the most common commercially available molecular testing in thyroid cancer, focusing on the technical features and test performance validation. Data Sources.— Peer-reviewed original articles, review articles, and published conference abstracts were reviewed to analyze the advantages and limitations of the most common tests used in the evaluation of thyroid needle aspirations. Conclusions.— The most common tests available include the Afirma Gene Expression Classifier, ThyGenX, and ThyroSeq. The excellent negative predictive value (NPV) of the Afirma test allows it to be used as a “rule out” test. ThyGenX analyzes a panel of DNA mutations and RNA translocation fusion markers to assess the risk of malignancy with good NPV and positive predictive value. ThyroSeq is a next-generation sequencing–based gene mutation and fusion test that has been reported to have the best NPV and positive predictive value combined, suggesting that it can be used as a “rule in” and “rule out” test. Molecular testing of cytology specimens from thyroid nodules has the potential to play a major role in the evaluation of indeterminate thyroid lesions.

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“…Sporadic medullary thyroid carcinomas with wild-type RET genes may harbor RAS mutations (HRAS or KRAS). 2,4,5,8,15,16 D. PIK3CA, AKT1, and TP53 Mutational Analysis PIK3CA, AKT1, and TP53 mutations are usually found in advanced thyroid cancer with propensity for dedifferentiation and distant metastasis. 8,17 E. CTNNB1 Mutational Analysis…”

Section: Ras Mutational Analysismentioning

confidence: 99%

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Thyroid Carcinoma

Chiosea

Sylvia

Berman

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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Targeted Next-Generation Sequencing Panel (ThyroSeq) for Detection of Mutations in Thyroid Cancer

Cited by 428 publications

References 56 publications

Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Thyroid Carcinoma

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