scholarly journals The genetic landscape of benign thyroid nodules revealed by whole exome and transcriptome sequencing

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Lei Ye ◽  
Xiaoyi Zhou ◽  
Fengjiao Huang ◽  
Weixi Wang ◽  
Yicheng Qi ◽  
...  
Keyword(s):  
Transcriptome Sequencing ◽  
Expression Patterns ◽  
Molecular Signature ◽  
Sequencing Data ◽  
Phylogenetic Tree Analysis ◽  
Whole Exome ◽  
Genetic Landscape ◽  
Benign Nodules ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Abstract The genomic alterations for benign thyroid nodule, especially adenomatoid nodule, one of the most common types of hyperplasia lesion, are ill-studied. Here, we show whole-exome sequencing and/or transcriptome sequencing data on adenomatoid nodules with or without coincidental papillary thyroid carcinoma (PTC). Somatic mutation of BRAF (22/32) is only detected in PTC, while mutations in SPOP (4/38), ZNF148 (6/38) and EZH1 (3/38) are found enriched in adenomatoid nodule. In an expanded cohort of adenomatoid nodule (n=259) mutually exclusive SPOP P94R , EZH1 Q571R and ZNF148 mutations are identified in 24.3% of them. Adenomatoid nodules show very few overlapped mutations and distinct gene expression patterns with their coincidental PTC. Phylogenetic tree analysis uncovers that PTCs evolved independently from their matched benign nodules. Our findings reveal that benign nodules possess a unique molecular signature that differs from PTC and provide genomic evidence for the conventional belief that PTC and benign nodules have independent origin.

Circulating Cytokeratin 19 Fragments in Patients with benign Nodules and Carcinomas of the Thyroid Gland

2008 ◽  
Vol 23 (1) ◽  
pp. 54-57 ◽  
Author(s):  
L. Giovanella ◽  
L. Ceriani ◽  
A. Ghelfo ◽  
M. Maffioli
Keyword(s):  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Differentiated Thyroid Carcinoma ◽  
Cytokeratin 19 ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Benign Nodules ◽  
Thyroid Malignancies ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 (Cyfra 21.1) can be measured by immunometric assays employing specific monoclonal antibodies. The present study was planned to assess the serum expression of Cyfra 21.1 in patients with benign thyroid nodules and thyroid malignancies. We enrolled 135 patients with histologically proven benign thyroid nodules (n=79) and thyroid carcinomas (n=56). No differences were found in serum Cyfra 21.1 levels between patients with benign nodules and patients with carcinomas. When thyroid malignancies were subdivided according to tumor histology, serum Cyfra 21.1 increased significantly from classical differentiated thyroid carcinomas (papillary or follicular) to less differentiated or undifferentiated carcinomas (poorly differentiated or anaplastic). CK19 release into the bloodstream is strongly related to the apoptotic pathway, and particularly to hyperproliferation-related apoptosis. These pathways characterized anaplastic and poorly differentiated thyroid carcinoma but not classical forms of differentiated thyroid carcinoma. Consequently, Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. Additionally, a role of Cyfra 21.1 as a dedifferentiation marker in patients with classical differentiated thyroid carcinomas may be postulated and should be explored by further focused studies.

Whole Exome Sequencing of Type 1 and Type 2 Enteropathy-Associated T Cell Lymphoma Reveals Genetic Basis of Eatl Oncogenesis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 575-575
Author(s):  
Sarah Lynn Ondrejka ◽  
Andrea B. Moffitt ◽  
Eric Tse ◽  
Eric D. Hsi ◽  
John R. Goodlad ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Somatic Mutations ◽  
Cell Lymphoma ◽  
Expression Patterns ◽  
T Cell Lymphoma ◽  
Sequencing Data ◽  
Whole Exome

Abstract Introduction Enteropathy-associated T cell lymphoma (EATL) is an intestinal tumor of the intraepithelial T lymphocytes, with a median survival time of less than 1 year. It is a rare disease in general and has two main subtypes described. Type 1 EATL is a complication in patients with celiac disease, a chronic gluten-sensitive enteropathy. Type 2 EATL, characterized by smaller monomorphic lymphocytes, typically occurs sporadically in patients without celiac disease. Very little is known about the genetic mutations and gene expression signatures that define this disease, or the extent to which the two types of EATL are genetically distinct. It has been suggested that the two types of EATLs should be reclassified as separate diseases in future WHO categories. Methods In this study, we performed whole exome sequencing to 100-fold depth of 41 EATL tumors including 23 type 1 cases and 18 type 2 cases. Both alpha-beta (65%) and gamma-delta (35%) T cell receptor rearrangements were seen among these cases. Paired normal DNA was sequenced in most (N=30) cases. We defined somatic mutations, copy number alterations, and HLA genotypes in these cases from sequencing data. Additionally, we generated RNA sequencing data on the same EATL tumors. Corresponding clinical and outcome data was collected on the same cohort. Results We found that both type 1 and type 2 EATLs had overlapping patterns of mutations and similar overall survival. The most commonly mutated genes were chromatin modifier genes (34%) including ATRX and ARID1B. We also identified recurrent somatic mutations in signal transduction genes, including JAK1 and BCL9L. TP53 mutations were also recurrent (12%). Copy number amplifications in 9q, 1q, and 8q occurred most frequently and were present in both subtypes. We further compared the mutational profiles to peripheral T cell lymphoma, angioimmunoblastic T cell lymphoma, cutaneous T cell lymphoma, natural killer/T cell lymphoma, diffuse large B cell lymphoma, and Burkitt lymphoma. These comparisons identify EATL as a genetically distinct disease with a very different pattern of mutations. RNAseq identified the gene expression patterns that are unique to EATL and also identified gene expression signatures that distinguish the two types of EATL. The DQ2 or DQ8 HLA genotype is present in the majority of type 1 cases (73%) while occurring infrequently in type 2 cases (27%). Conclusions Our study defines the genetic landscape of enteropathy associated T cell lymphoma and highlights the genetic and clinical overlap between the two types. While the two types have differences in mutations and gene expression patterns, they have more in common with each other compared to other lymphoma types. Our data may inform future decisions regarding the potential separation of the two EATL types as distinct entities. Disclosures No relevant conflicts of interest to declare.

scholarly journals Benign Aspirates on Follow-Up FNA May Be Enough in Patients with Initial Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ga Ram Kim ◽  
Jung Hyun Yoon ◽  
Eun-Kyung Kim ◽  
Hee Jung Moon ◽  
Jin Young Kwak
Keyword(s):  
Thyroid Nodules ◽  
Surgical Excision ◽  
Needle Aspiration ◽  
Risk Of Malignancy ◽  
Benign Nodules ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid ◽  
Undetermined Significance

Background.Management of thyroid nodules with benign aspirates following atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is not well established. We reviewed the risk of malignancy and the role of ultrasound (US) features among thyroid nodules with benign results following initial AUS/FLUS diagnoses.Methods.From December 2009 to February 2011, a total of 114 nodules in 114 patients diagnosed as benign on follow-up fine-needle aspiration (FNA) after AUS/FLUS results were included in our study. Eight among 114 nodules were confirmed pathologically and 106 were clinically observed by a follow-up FNA or US. Suspicious US features were defined as markedly hypoechogenicity, irregular or microlobulated margin, presence of microcalcifications, and taller than wide shape.Results.There were 110 (96.5%) benign nodules and 4 (3.5%) malignant nodules. Two (4.8%) among 42 nodules without suspicious US features and 2 (2.8%) out of 72 nodules with suspicious US features were confirmed as malignancy, but there were no significant associations between the malignancy rate and US features (P=0.625).Conclusion.Clinical follow-up instead of surgical excision or continuous repeat FNA may be enough for benign thyroid nodules after AUS/FLUS. The role of US features might be insignificant in the management of these nodules.

scholarly journals Comparative efficacy of different ultrasound-guided ablation for the treatment of benign thyroid nodules: Systematic review and network meta-analysis of randomized controlled trials

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0243864
Author(s):  
Linye He ◽  
Wanjun Zhao ◽  
Zijing Xia ◽  
Anping Su ◽  
Zhihui Li ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Volume Change ◽  
Thyroid Nodules ◽  
Meta Analysis ◽  
Percutaneous Ablation ◽  
Score Change ◽  
Benign Nodules ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Background Percutaneous ablation is currently deemed an additionally treatment option for benign thyroid nodules in the world, but possibly different effect among the ablation modalities is not clear. So we aim to evaluate the efficacy and complications of thermal/chemical ablation by network meta-analysis. Materials and methods In the network meta-analysis, PubMed, EMBASE and the Cochrane Library databases were searched from 1980 to 2020. Studies of adults with thyroid benign nodules under percutaneous ablation therapy were included. Percentage mean volume change, symptom score change, cosmetic score change and complications were evaluated by network meta-analysis. Results In the network meta-analysis, Radiofrequency Ablation(RFA) with 2 treatment sessions group was associated with the highest reduction for the mean volume change during 6-month follow-up (MD = 79.09 and 95% CrI:48.23–89.94). There is no significant difference in the incidence of complications. Subgroup analysis showed that 2 sessions of Radiofrequency Ablation (RFA) ranks the highest probability (surface under the cumulative ranking curve (SUCRA) values 77.9) of being the most efficacious treatment for solid or predominantly solid benign nodules. Ethanol ablation (EA) ranked first (SUCRA value 81.1) in the treatment for cyst or predominantly cyst benign nodules. Conclusion RFA appears to be superior to other US-guided percutaneous ablation in reducing benign thyroid nodule volume during short- and long-term follow-up. In the subgroup analysis, RFA with 2 treatment sessions showed the most significant effectiveness for solid benign thyroid nodules and EA showed more effectiveness to decrease the volume of cyst benign thyroid nodules.

scholarly journals Characterization of benign thyroid nodules with HyperSPACE (Hyper Spectral Analysis for Characterization in Echography) before and after percutaneous laser ablation: a pilot study

2017 ◽  
Vol 19 (2) ◽  
pp. 172 ◽  
Author(s):  
Simona Granchi ◽  
Enrico Vannacci ◽  
Elena Biagi
Keyword(s):  
Spectral Analysis ◽  
Laser Treatment ◽  
Tissue Characterization ◽  
Thyroid Nodules ◽  
Additional Information ◽  
Hyper Spectral ◽  
Before And After ◽  
Benign Nodules ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Aims: To evaluate the capability of the HyperSPACE (Hyper SPectral Analysis for Characterization in Echography) method in tissue characterization, in order to provide information for the laser treatment of benign thyroid nodules in respect of conventional B-mode images and elastography.Material and methods: The method, based on the spectral analysis of the raw radiofrequency ultrasonic signal, was applied to characterize the nodule before and after laser treatment. Thirty patients (25 females and 5 males, age between 37 and 81 years) with thyroid benign nodule at cytology (Thyr 2) were evaluated by conventional ultrasonography, elastography, and HyperSPACE, before and after laser ablation.Results: The images processed by HyperSPACE exhibit different color distributions that are referred to different tissue features. By calculating the percentages of the color coverages, the analysed nodules were subdivided into 3 groups. Each nodule belonging to the same group experienced, on average, similar necrosis extension. The nodules exhibit different Configurations (colors) distributions that could be indicative of the response of nodular tissue to the laser treatmentConclusions: HyperSPACEcan characterize benign nodules by providing additional information in respect of conventional ultrasound and elastography which is useful for support in the laser treatment of nodules in order to increase the probability of success.

scholarly journals Integrated Whole-Exome and Transcriptome Sequencing of Sporadic Parathyroid Adenoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Ya Hu ◽  
Xiang Zhang ◽  
Ou Wang ◽  
Ming Cui ◽  
Xiaobin Li ◽  
...  
Keyword(s):  
Parathyroid Adenoma ◽  
Molecular Mechanism ◽  
Clustering Analysis ◽  
Transcriptome Sequencing ◽  
Gene Mutations ◽  
Driver Gene ◽  
Consensus Clustering ◽  
Rna Seq ◽  
Sequencing Data ◽  
Whole Exome

PurposeHyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA.MethodsWhole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed.ResultsPreviously reported PA driver gene mutations, such as MEN1 (9/41), mTOR (4/41), ZFX (3/41), CASR (3/41), EZH2 (2/41) and FAT1 (2/41), were also identified in our cohort. Furthermore, somatic mutation of EZH1, which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes.ConclusionMEN1, EZH2, CASR, EZH1, ZFX, mTOR and FAT1 mutations in PA were revealed. According to the RNA-seq data clustering analysis, cyclin D1, β-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression profile.

scholarly journals Growth rates of malignant and benign thyroid nodules in an ultrasound follow-up study: a retrospective cohort study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Michael Cordes ◽  
Theresa Ida Götz ◽  
Karen Horstrup ◽  
Torsten Kuwert ◽  
Christian Schmidkonz
Keyword(s):  
Growth Rates ◽  
Thyroid Nodules ◽  
Cellular Proliferation ◽  
Significance Level ◽  
Follow Up Study ◽  
Benign Nodules ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid ◽  
Volumetric Measurements

Abstract Background Thyroid nodules are frequently detected by cervical ultrasound examinations. In follow-up studies, malignant as well as benign nodules may exhibit an increase in size. The objective of our investigation was to test whether histologically determined malignant and benign thyroid nodules show differences in growth rates above a defined significance level. Methods A retrospective ultrasound cohort follow-up study from 4 to 132 months included 26 patients with differentiated carcinomas and 26 patients with adenomas of the thyroid gland. Significance levels were determined by intra- and interobserver variations of volumetric measurements in 25 individuals. Results Intra- and interobserver volumetric measurements were highly correlated (r = 0.99 and r = 0.98, respectively), with variations of 28 and 40%, respectively. The growth rates of malignant and benign nodules did not show differences with respect to two sonographic measurements (d = − 0.04, 95%CI(P): 0.41–0.85, P = 0.83). Using shorter increments and multiple measurements, growth rates of malignant nodules revealed significantly higher values (d = 0.16, 95%CI(P): 0.02–0.04, P = 0.039). Conclusions The growth rates of benign and malignant thyroid nodules do not appear to differ using two sonographic volumetric measurements. However, due to temporal changes in cellular proliferation and arrest, malignant nodules may exhibit higher growth rates with multiple assessments and shorter increments.

Radiofrequency Thermal Ablation of Benign Thyroid Nodules: The Correlation Between Ultrasound Nodule Characteristics and Results

2020 ◽  
pp. 155335062091313
Author(s):  
Francesco Feroci ◽  
Tommaso Guagni ◽  
Angela Coppola ◽  
Davina Perini ◽  
Barbara Conforti ◽  
...  
Keyword(s):  
Thermal Ablation ◽  
Thyroid Nodules ◽  
Reduction Rate ◽  
Response To Treatment ◽  
Initial Size ◽  
Benign Nodules ◽  
Benign Thyroid Nodules ◽  
Radiofrequency Thermoablation ◽  
Benign Thyroid

Background. The aim of this observational study was to investigate for which nodules a better response to radiofrequency thermoablation (RFA) for nonfunctioning benign thyroid nodules is likely. Methods. Aesthetic score, compressive score, and volume of 32 benign nodules from 32 patients were registered during follow-up at baseline, 1, 3, 6, and 12 months. Results. A volume reduction rate (VRR) of 72.56% at 12 months after the procedure ( P = .009) was registered. A significant ( P < .001) improvement in the compressive and aesthetic scores was observed. Nodules with a baseline volume <20 mL had VRRs at 3 and 6 months that were significantly greater than those with volume >20 mL ( P = .037). Conclusions. RFA was shown to be a safe and effective procedure for the management of benign thyroid nodules and that there is a correlation between the initial size of the nodule and the response to treatment.

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