Description of a New miRNA Signature for the Surgical Management of Thyroid Nodules.

Background: The diagnosis of malignant thyroid nodules is mainly based on the fine-needle aspiration biopsy (FNAB). To improve the detection of malignant nodules, different molecular tests have been developed. We present a new molecular signature based on altered miRNA expressions and specific mutations.

Understanding the Dosage-Dependent Role of in Thyroid Tumorigenesis.

Tumors originating from thyroid follicular cells are the most common endocrine tumors, with rising incidence. Despite a generally good prognosis, up to 20% of patients experience recurrence and persistence, highlighting the need to identify the underlying molecular mechanisms. has been found to be altered in papillary thyroid cancer (PTC).

CDK4 phosphorylation status and rational use for combining CDK4/6 and BRAF/MEK inhibition in advanced thyroid carcinomas.

Background: CDK4/6 inhibitors (CDK4/6i) have been established as standard treatment against advanced Estrogen Receptor-positive breast cancers. These drugs are being tested against several cancers, including in combinations with other therapies. We identified the T172-phosphorylation of CDK4 as the step determining its activity, retinoblastoma protein (RB) inactivation, cell cycle commitment and sensitivity to CDK4/6i.

Unraveling the Roles of miR-204-5p and HMGA2 in Papillary Thyroid Cancer Tumorigenesis.

Thyroid cancer is the most common endocrine malignant tumor with an increasing incidence rate. Although differentiated types of thyroid cancer generally present good clinical outcomes, some dedifferentiate into aggressive and lethal forms. However, the molecular mechanisms governing aggressiveness and dedifferentiation are still poorly understood.

Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications.

Though heterogeneity of cancers is recognized and has been much discussed in recent years, the concept often remains overlooked in different routine examinations. Indeed, in clinical or biological articles, reviews, and textbooks, cancers and cancer cells are generally presented as evolving distinct entities rather than as an independent heterogeneous cooperative cell population with its self-oriented biology. There are, therefore, conceptual gaps which can mislead the interpretations/diagnostic and therapeutic approaches.

Thyroid cancer under the scope of emerging technologies.

The vast majority of thyroid cancers originate from follicular cells. We outline outstanding issues at each step along the path of cancer patient care, from prevention to post-treatment follow-up and highlight how emerging technologies will help address them in the coming years. Three directions will dominate the coming technological landscape.

Transcriptomic Signature of Human Embryonic Thyroid Reveals Transition From Differentiation to Functional Maturation.

The human thyroid gland acquires a differentiation program as early as weeks 3-4 of embryonic development. The onset of functional differentiation, which manifests by the appearance of colloid in thyroid follicles, takes place during gestation weeks 10-11. By 12-13 weeks functional differentiation is accomplished and the thyroid is capable of producing thyroid hormones although at a low level.

Dissecting the Role of Thyrotropin in the DNA Damage Response in Human Thyrocytes after 131I, γ Radiation and H2O2.

Background: The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes.

Methods: Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (β radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status.

Class III PI3K Vps34 Controls Thyroid Hormone Production by Regulating Thyroglobulin Iodination, Lysosomal Proteolysis, and Tissue Homeostasis.

The production of thyroid hormones [triiodothyronine (T3), thyroxine (T4)] depends on the organization of the thyroid in follicles, which are lined by a monolayer of thyrocytes with strict apicobasal polarity. This polarization supports vectorial transport of thyroglobulin (Tg) for storage into, and recapture from, the colloid. It also allows selective addressing of channels, transporters, ion pumps, and enzymes to their appropriate basolateral [Na/I symporter (NIS), SLC26A7, and Na/K-ATPase] or apical membrane domain (anoctamin, SLC26A4, DUOX2, DUOXA2, and thyroperoxidase).

Reprogramming of Energy Metabolism: Increased Expression and Roles of Pyruvate Carboxylase in Papillary Thyroid Cancer.

Energy metabolism is described to be deregulated in cancer, and the Warburg effect is considered to be a major hallmark. Recently, cellular heterogeneity in tumors and the tumor microenvironment has been recognized to play an important role in several metabolic pathways in cancer. However, its contribution to papillary thyroid cancer (PTC) development and metabolism is still poorly understood.

Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution.

Non-autonomous thyroid nodules are common in the general population with a proportion found to be cancerous. A current challenge in the field is to be able to distinguish benign adenoma (FA) from preoperatively malignant thyroid follicular carcinoma (FTC), which are very similar both histologically and genetically. One controversial issue, which is currently not understood, is whether both tumor types represent different molecular entities or rather a biological continuum.

Distinctive Desmoplastic 3D Morphology Associated With BRAFV600E in Papillary Thyroid Cancers.

Context: Although 60% of papillary thyroid carcinomas are BRAFV600E mutant (PTCV600E), the increased aggressiveness of these cancers is still debated.

Objective: For PTCV600E we aimed to further characterize the extent of the stroma and its activation, the three-dimensional (3D) tumor-stroma interface, and the proliferation rates of tumor and stromal fibroblasts.

Design: We analyzed exomes, transcriptomes, and images of 364 papillary thyroid carcinoma (PTCs) from The Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTCs for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary tumor blocks and 4 nodal metastases from one patient with PTCV600E; and reconstructed the 3D volumes of one tumor and one metastatic block at histological resolution.

Cancer heterogeneity is not compatible with one unique cancer cell metabolic map.

The Warburg effect and its accompanying metabolic features (anaplerosis, cataplerosis) are presented in textbooks and reviews as a hallmark (general characteristic): the metabolic map of cancer. On the other hand, research articles on specific tumors since a few years emphasize various biological features of different cancers, different cells in a cancer and the dynamic heterogeneity of these cells. We have analysed the research literature of the subject and show the generality of a dynamic, evolving biological and metabolic, spatial and temporal heterogeneity of individual cancers.

ApolipoproteinL1 is expressed in papillary thyroid carcinomas.

The apolipoprotein L (apoL) family has not yet been ascribed any definite patho-physiological function although the conserved BH3 protein domain suggests a role in programmed cell death. As repression of the regular apoptotic program is considered a hallmark of tumor progression, we investigated apoL expression in cancer. We show that the levels of one member of the family, apolipoprotein L1 (apoL1) is higher in papillary thyroid carcinoma compared to normal tissue.

Gene signature of the post-Chernobyl papillary thyroid cancer.

Purpose: Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC.

Methods: We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.

New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer.

Background: Papillary Thyroid Cancer (PTC) is the most prevalent type of endocrine cancer. Its incidence has rapidly increased in recent decades but little is known regarding its complete microRNA transcriptome (miRNome). In addition, there is a need for molecular biomarkers allowing improved PTC diagnosis.

Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer.

Background: Transcriptome profiling has helped characterise nodal spread. The interpretation of these data, however, is not without ambiguities.

Methods: We profiled the transcriptomes of papillary thyroid cancer nodal metastases, associated primary tumours and primary tumours from N0 patients.

microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation.

The objective of the study was to identify the deregulated miRNA in autonomous adenoma and to correlate the data with mRNA regulation. Seven autonomous adenoma with adjacent healthy thyroid tissues were investigated. Twelve miRNAs were downregulated and one was upregulated in the tumors.

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases.

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases.

MiRNA expression may account for chronic but not for acute regulation of mRNA expression in human thyroid tumor models.

Background: For thyroid tumorigenesis, two main human in vitro models are available: primary cultures of human thyrocytes treated with TSH or EGF/serum as models for autonomous adenomas (AA) or papillary thyroid carcinomas (PTC) respectively, and human thyroid tumor derived cell lines. Previous works of our group have assessed properties of those models, with a special emphasis on mRNA regulations. It is often assumed that miRNA may be one of the primary events inducing these mRNA regulations.

miRNA expression in anaplastic thyroid carcinomas.

Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents an end stage of thyroid tumor progression. No effective treatment exists so far. In this study, we analyzed the miRNA expression profiles of 11 ATC by microarrays and their relationship with the mRNA expression profiles of the same 11 ATC samples.