BRAFV600E Mutation Does Not Significantly Affect the Efficacy of Radioiodine Therapy in Patients With Papillary Thyroid Carcinoma Without Known Distant Metastases

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.

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An Adolescent with Papillary Thyroid Carcinoma and Locally Metastatic Disease but No Distant Metastases

Thyroid Cancer ◽

10.1007/978-3-030-61919-0_11 ◽

2020 ◽

pp. 93-102

Author(s):

Sarah J. Bottomley ◽

Steven G. Waguespack

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Metastatic Disease ◽

Distant Metastases ◽

Papillary Thyroid

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Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma

Nature Communications ◽

10.1038/s41467-021-26343-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Weilin Pu ◽

Xiao Shi ◽

Pengcheng Yu ◽

Meiying Zhang ◽

Zhiyan Liu ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Single Cell ◽

Epithelial Mesenchymal Transition ◽

Distant Metastases ◽

Developmental Trajectory ◽

Papillary Thyroid ◽

Normal Morphology ◽

Mesenchymal Transition ◽

Therapeutic Implications

AbstractThe tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.

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The ratio of BRAFV600E alleles can be used to assess the biological behavior of papillary thyroid carcinoma

10.1101/2020.10.31.20223610 ◽

2020 ◽

Author(s):

Dingcun Luo ◽

Yeqin Ni ◽

Shirong Zhang ◽

Yanping Xun ◽

Pan Zhao ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Tumor Recurrence ◽

Recurrence Risk ◽

Tumor Stage ◽

Biological Behavior ◽

Clinicopathological Parameters ◽

Quantitative Detection ◽

Papillary Thyroid ◽

Brafv600e Mutation

ABSTRACTBackgroundThe BRAFV600E mutations is an important molecular event in the occurrence and development of papillary thyroid carcinoma (PTC). A qualitative detection of the BRAFV600E mutation is still insufficient to explain the biological behavior of PTC. Though quantitative detection of the BRAFV600E mutation can reflect certain characteristics of PTC, its clinical value is still controversial. We aimed to investigate the association between the ratio of BRAFV600E alleles and clinicopathological parameters in PTC patients.MethodsGenomic DNA was extracted from specimens obtained from 329 PTC patients undergoing thyroidectomy. The ratio of BRAFV600E alleles was determined by amplification refractory mutation system (ARMS) and droplet digital polymerase chain reaction (ddPCR). Inconsistent results were further verified by next-generation sequencing (NGS). The clinicopathologic features, clinical tumor stage, and tumor recurrence risk stratification of all patients were correlated with the ratio of BRAFV600E alleles.ResultsThe sensitivity of ddPCR was superior to that of ARMS and almost the same as that of NGS. In total, 275 of 329 patients had the BRAFV600E mutation as determined by ARMS, ddPCR and NGS. The ratio of BRAFV600E alleles ranged from 0.17%-48.0%, with a median ratio of 12.58%, and significantly correlated with tumor size (p<0.001), capsule or extrathyroidal invasion (p<0.001), the number or rate of lymph node metastases (p<0.001), tumor stage (p=0.006) and tumor recurrence risk (p<0.001) but not with sex, age or multifocality. The ratio of BRAFV600E alleles was much lower in PTC patients with Hashimoto’s thyroiditis than in those without (p<0.001).ConclusionsThe ratio of BRAFV600E alleles can reliably reflect the biological behavior of PTC, making it a molecular-based stratification index of recurrence risk. The quantitative detection of BRAFV600E has the potential to guide the clinical diagnosis and treatment of PTC.

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TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma

Acta Endocrinologica ◽

10.1530/eje-14-0837 ◽

2015 ◽

Vol 172 (4) ◽

pp. 403-413 ◽

Cited By ~ 70

Author(s):

Greta Gandolfi ◽

Moira Ragazzi ◽

Andrea Frasoldati ◽

Simonetta Piana ◽

Alessia Ciarrocchi ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Direct Sequencing ◽

Distant Metastases ◽

Braf V600e ◽

Papillary Thyroid ◽

Mutational Status ◽

Metastatic Behavior ◽

Well Differentiated ◽

Promoter Mutations

ObjectiveTranscriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were reported at high frequency in aggressive poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance of these mutations in the metastatic behavior of well-differentiated thyroid cancer is still to be defined. The aim of this work was to investigate the frequency ofTERTpromoter mutations in a remarkable cohort of well-differentiated papillary thyroid carcinoma that developed distant metastases (DM-PTCs) and to establish whether these mutations may be predictive of metastatic behavior.DesignWe analyzed the frequency ofTERTpromoter mutations in a group of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a group of 78 PTCs without distant metastases (control-PTCs). The possible correlation betweenTERTpromoter mutations and BRAF V600E mutation was also investigated.MethodsTERTpromoter mutational status was evaluated by direct sequencing of the hotspot harboring the C228T and the C250T mutations.ResultsIn the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a mutation in theTERTpromoter. Noticeably, 33% of DM-PTCs were mutated in theTERTpromoter while only 9% of the control-PTCs showed a mutation in this locus. We also observed a positive association between BRAF V600E andTERTC228T mutations in the cohort of DM-PTCs.ConclusionsThese results indicate thatTERTpromoter mutations are associated with the development of distant metastases in PTCs and may help in predicting aggressive behavior in this type of tumor.

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