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1.
Am J Med Genet A ; 179(6): 966-977, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30920161

RESUMEN

Phacomatosis pigmentovascularis (PPV) comprises a family of rare conditions that feature vascular abnormalities and melanocytic lesions that can be solely cutaneous or multisystem in nature. Recently published work has demonstrated that both vascular and melanocytic abnormalities in PPV of the cesioflammea and cesiomarmorata subtypes can result from identical somatic mosaic activating mutations in the genes GNAQ and GNA11. Here, we present three new cases of PPV with features of the cesioflammea and/or cesiomarmorata subtypes and mosaic mutations in GNAQ or GNA11. To better understand the risk of potentially occult complications faced by such patients we additionally reviewed 176 cases published in the literature. We report the frequency of clinical findings, their patterns of co-occurrence as well as published recommendations for surveillance after diagnosis. Features assessed include: capillary malformation; dermal and ocular melanocytosis; glaucoma; limb asymmetry; venous malformations; and central nervous system (CNS) anomalies, such as ventriculomegaly and calcifications. We found that ocular findings are common in patients with phacomatosis cesioflammea and cesiomarmorata. Facial vascular involvement correlates with a higher risk of seizures (p = .0066). Our genetic results confirm the role of mosaic somatic mutations in GNAQ and GNA11 in phacomatosis cesioflammea and cesiomarmorata. Their clinical and molecular findings place these conditions on a clinical spectrum encompassing other GNAQ and GNA11 related disorders and inform recommendations for their management.


Asunto(s)
Síndromes Neurocutáneos/diagnóstico , Fenotipo , Alelos , Niño , Diagnóstico Diferencial , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Genotipo , Humanos , Lactante , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Mutación , Síndromes Neurocutáneos/genética , Piel/patología , Secuenciación del Exoma
2.
RNA ; 19(1): 51-62, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23169800

RESUMEN

Profiling of mRNA abundances with high-throughput platforms such as microarrays and RNA-seq has become an important tool in both basic and biomedical research. However, these platforms remain prone to systematic errors and have challenges in clinical and industrial applications. As a result, it is standard practice to validate a subset of key results using alternate technologies. Similarly, clinical and industrial applications typically involve transitions from a high-throughput discovery platform to medium-throughput validation ones. These medium-throughput validation platforms have high technical reproducibility and reduced sample input needs, and low sensitivity to sample quality (e.g., for processing FFPE specimens). Unfortunately, while medium-throughput platforms have proliferated, there are no comprehensive comparisons of them. Here we fill that gap by comparing two key medium-throughput platforms--NanoString's nCounter Analysis System and ABI's OpenArray System--to gold-standard quantitative real-time RT-PCR. We quantified 38 genes and positive and negative controls in 165 samples. Signal:noise ratios, correlations, dynamic range, and detection accuracy were compared across platforms. All three measurement technologies showed good concordance, but with divergent price/time/sensitivity trade-offs. This study provides the first detailed comparison of medium-throughput RNA quantification platforms and provides a template and a standard data set for the evaluation of additional technologies.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Animales , Perfilación de la Expresión Génica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/economía , Secuenciación de Nucleótidos de Alto Rendimiento/instrumentación , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Dibenzodioxinas Policloradas/toxicidad , ARN Mensajero/efectos de los fármacos , Ratas , Ratas Long-Evans , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa/economía , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación , Reproducibilidad de los Resultados , Relación Señal-Ruido
3.
Oncotarget ; 6(6): 4537-50, 2015 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-25738365

RESUMEN

PURPOSE: Despite significant improvement in locoregional control in the contemporary era of nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a significant risk of distant metastasis (DM). Identifying those patients at risk of DM would aid in personalized treatment in the future. MicroRNAs (miRNAs) play many important roles in human cancers; hence, we proceeded to address the primary hypothesis that there is a miRNA expression signature capable of predicting DM for NPC patients. METHODS AND RESULTS: The expression of 734 miRNAs was measured in 125 (Training) and 121 (Validation) clinically annotated NPC diagnostic biopsy samples. A 4-miRNA expression signature associated with risk of developing DM was identified by fitting a penalized Cox Proportion Hazard regression model to the Training data set (HR 8.25; p < 0.001), and subsequently validated in an independent Validation set (HR 3.2; p = 0.01). Pathway enrichment analysis indicated that the targets of miRNAs associated with DM appear to be converging on cell-cycle pathways. CONCLUSIONS: This 4-miRNA signature adds to the prognostic value of the current "gold standard" of TNM staging. In-depth interrogation of these 4-miRNAs will provide important biological insights that could facilitate the discovery and development of novel molecularly targeted therapies to improve outcome for future NPC patients.


Asunto(s)
MicroARNs/análisis , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Transcriptoma , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Carcinoma , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Curva ROC , Adulto Joven
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