Intestinal-Type Adenocarcinoma in Head and Neck: Dissecting Oncogenic Gene Alterations Through Whole Transcriptome and Exome Analysis.

Adenocarcinomas of the nasal/paranasal sinuses are uncommon, but intestinal-type adenocarcinomas (ITACs) are important. Due to the rarity of these tumors, their molecular profile is not well known. To further investigate the molecular profile and find potential oncogenic drivers, we compared the whole transcriptome and exome of ITACs at different anatomic locations in the head and neck.

High-grade sinonasal carcinomas and surveillance of differential expression in immune related transcriptome.

The skull base is the location of a wide variety of malignant tumors. Among them is sinonasal undifferentiated carcinoma (SNUC), a highly aggressive sinonasal neoplasm that was recently reclassified into subgroups of high-grade carcinomas with unique genomic events (e.g.

Magnifying glass on spiradenoma and cylindroma histogenesis and tumorigenesis using systematic transcriptome analysis.

Spiradenoma and cylindroma are related sweat gland tumors. To delineate their histogenesis, gene profiles, and their potential drivers, we performed a whole-transcriptome sequencing analysis of fourteen samples of spiradenoma/cylindroma in comparison to normal samples. A total of 12 spiradenomas, 5 cylindromas, 3 hybrid spiradenomas/cylindromas and 2 adnexal carcinomas were included in this study.

Comparative transcriptome analysis of sinonasal inverted papilloma and associated squamous cell carcinoma: Out-HOXing developmental genes.

Background: Sinonasal papilloma has a tendency toward local destruction, recurrence, and malignant transformation. This study aimed to unravel mechanisms in the malignant transformation of sinonasal papillomas using RNA-seq.

Methods: The cohort consisted of 37 consecutive patients; tumor histology included a continuum spectrum (sinonasal papillomas/dysplastic/carcinomas-in-situ/invasive squamous cell carcinomas).

Detection of a MicroRNA molecular signature of ultraviolet radiation in the superficial regions of melanocytic nevi on sun-exposed skin.

How melanocytes transform into melanoma cells remains largely unknown. However, prolonged ultraviolet radiation exposure is linked with melanoma, and the DNA of melanomas arising in chronically sun-exposed skin is characterized by an elevated number of pyrimidine transitions, mainly C>T (predominantly caused by ultraviolet B), and transversions of GC>TA or AT>CG (caused by ultraviolet A over indirect mechanisms). Since ultraviolet penetrates mostly only the superficial dermis, we sought to determine the extent to which superficial and deep melanocytes of nevi in sun-exposed skin differ in their miRNA expression and consider the changes as likely secondary to ultraviolet radiation-induced damage.

Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas.

Chordomas are rare, slowly growing, locally aggressive bone neoplasms that arise from embryonic remnants of the notochord, showing dual epithelial-mesenchymal differentiation. The high plasticity probably is the main reason for the high variety in phenotypes of chordoma, from its high heterogeneity on a cellular level to its subtype variations depending on tissue location, with its potential to develop from an inactive quiescent form to an aggressive cancer with extreme adaptability and resistance to drugs and other treatments. Gene expression profiles of formalin-fixed, paraffin-embedded skull chordoma, spine chordoma, and normal tissue specimens were generated and compared.

Whole-transcriptome analysis of chordoma of the skull base.

Fourteen skull base chordoma specimens and three normal specimens were microdissected from paraffin-embedded tissue. Pools of RNA from highly enriched preparations of these cell types were subjected to expression profiling using whole-transcriptome shotgun sequencing. Using strict criteria, 294 differentially expressed transcripts were found, with 28 % upregulated and 72 % downregulated.

In-depth characterization of the salivary adenoid cystic carcinoma transcriptome with emphasis on dominant cell type.

Background: Adenoid cystic carcinoma (ACC), 1 of the most common salivary gland malignancies, arises from the intercalated ducts, which are composed of inner ductal epithelial cells and outer myoepithelial cells. The objective of this study was to determine the genomic subtypes of ACC with emphasis on dominant cell type to identify potential specific biomarkers for each subtype and to improve the understanding of this disease.

Methods: A whole-genome expression study was performed based on 42 primary salivary ACCs and 5 normal salivary glands.

Global transcriptome and sequenome analysis of formalin-fixed salivary epithelial-myoepithelial carcinoma specimens.

Diverse microarray and sequencing technologies have been widely used to characterize molecular changes in malignant epithelial cells in salivary neoplasms. Such gene expression studies to identify markers and targets in tumor cells are, however, compromised by the cellular heterogeneity of these tumors and by the difficulties to accrue matching controls representing normal salivary glands. Seventeen samples of primary salivary epithelial-myoepithelial carcinoma along with tissue from six normal major salivary glands were microdissected from paraffin-embedded tissue.

Nuclear plakoglobin is essential for differentiation of cardiac progenitor cells to adipocytes in arrhythmogenic right ventricular cardiomyopathy.

Rationale: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease of desmosome proteins characterized by fibroadipogenesis in the myocardium. We have implicated signaling properties of junction protein plakoglobin (PG) in the pathogenesis of ARVC.

Objective: To delineate the pathogenic role of PG in adipogenesis in ARVC.

Developmental transcription factor EN1--a novel biomarker in human salivary gland adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by histogenetic, morphologic, and clinical heterogeneity. Extensive efforts to characterize the molecular events associated with these tumors have included the identification of biomarkers for prognostication and post-therapy assessment. In a previous study of genome-wide methylation screening, the authors of the current report identified a limited number of differentially methylated gene regions in ACC, and significant hypermethylation was observed at the transcriptional start sites of genes that encode for the transcription factor engrailed homeobox 1 (EN1).

CpG island methylation profiling in human salivary gland adenoid cystic carcinoma.

Background: DNA methylation is a fundamental epigenetic event associated with physiologic and pathologic conditions, including cancer. Hypermethylation of CpG islands at active gene promoters leads to transcriptional repression, whereas hypomethylation is associated with gene overexpression. The aim of this study was to identify genes in adenoid cystic carcinoma (ACC) of salivary gland strongly deregulated by epigenetic CpG island methylation, to validate selected genes by conventional techniques, and to correlate the findings with clinicopathologic factors.

Genetic fate mapping identifies second heart field progenitor cells as a source of adipocytes in arrhythmogenic right ventricular cardiomyopathy.

The phenotypic hallmark of arrhythmogenic right ventricular cardiomyopathy, a genetic disease of desmosomal proteins, is fibroadipocytic replacement of the right ventricle. Cellular origin of excess adipocytes, the responsible mechanism(s) and the basis for predominant involvement of the right ventricle are unknown. We generated 3 sets of lineage tracer mice regulated by cardiac lineage promoters alpha-myosin heavy chain (alphaMyHC), Nkx2.

Differential interactions of thin filament proteins in two cardiac troponin T mouse models of hypertrophic and dilated cardiomyopathies.

Aim: Mutations in a sarcomeric protein can cause hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM), the opposite ends of a spectrum of phenotypic responses of the heart to mutations. We posit the contracting phenotypes could result from differential effects of the mutant proteins on interactions among the sarcomeric proteins. To test the hypothesis, we generated transgenic mice expressing either cardiac troponin T (cTnT)-Q92 or cTnT-W141, known to cause HCM and DCM, respectively, in the heart.

Isoflurane modulates genomic expression in rat amygdala.

General anesthesia, at a minimum, provides amnesia and unresponsiveness. Although anesthetics have many modulatory effects on neuronal ionophore protein complexes, it is not clear that the resulting electrophysiologic changes are the sole mechanisms of clinical anesthetic action. Cells respond to environmental changes in several ways, including alterations in DNA transcription leading to changes in the cell's proteins.

Presence of morphine in rat amygdala: evidence for the mu3 opiate receptor subtype via nitric oxide release in limbic structures.

Background: We have identified a novel mu opiate receptor, p3, which is expressed in several human tissues, is selective for opiate alkaloids, insensitive to opioid peptides, and also is coupled to constitutive nitric oxide release. We, and others, have also demonstrated the presence of opiate alkaloids as endogenous substances in various nerve tissues taken from mammals, man and invertebrates.

Material/methods: Morphine isolation and identification was achieved by high pressure liquid chromatography coupled to electrochemical detection.