Oncogenic GNAQ mutations are not correlated with disease-free survival in uveal melanoma

BackgroundRecently, oncogenic G protein alpha subunit q (GNAQ) mutations have been described in about 50% of uveal melanomas and in the blue nevi of the skin.MethodsGNAQ exon 5 was amplified from 75 ciliary body and choroidal melanoma DNAs and sequenced directly. GNAQ mutation status was correlated with disease-free survival (DFS), as well as other clinical and histopathological factors, and with chromosomal variations detected by FISH and CGH.ResultsOf the 75 tumour DNA samples analysed, 40 (53.3%) harboured oncogenic mutations in GNAQ codon 209. Univariate and multivariate analysis showed that GNAQ mutation status was not significantly correlated with DFS.ConclusionThe GNAQ mutation status is not suitable to predict DFS. However, the high frequency of GNAQ mutations may render it a promising target for therapeutic intervention

Biology of advanced uveal melanoma and next steps for clinical therapeutics.

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation\u27s ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed

Integrative Genome Comparison of Primary and Metastatic Melanomas

A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes

An OAI framework for biodiversity and contextual content: PlanktonNet as pilot study

Digital objects in the field of earth and biological sciences are known to be often compound and complex. If one takes biodiversity as example, an exhaustively long list of information systems can be found on-line. These systems often contain valuable and historically relevant information gathered over several decades using distinct archival resources, data models and transport protocols.In order to assure long term preservation of this distributed and not yet networked mass of information on worlds biota, we need to create an abstract interoperability layer in which digital objects sharing the same data model are aggregated so as to allow for information preservation, transformation, re-use and exchange . Using panFMP and FEDORA technologies, we propose a strategy for creating an information network for biodiversity and related contextual content (e.g., oceanographic data). A prototype for the proposed information network was built upon existing PlanktonNet data providers, publication repositories and environmental data archived in WDC-Mare/Pangaea. Because XML schemas for metadata description and for expressing relationships among digital objects are available, interoperability with other federated networks will be assured. In addition, a panFMP front-end customized specifically for PlanktonNet is presented as metadata porta

Prototypenentwicklung und ökonomischer Leistungsvergleich von OAI- und Web Service-orientierten Architekturen zur Realisierung von Repositories für Publikationen in einer wissenschaftlichen Großforschungseinrichtung

This work deals with Open Access and its implementation at the Alfred Wegener Institute; Bremerhaven. The existing system for archiving scientific publications has proved to be expensive and to lack the flexibility required in the Open Archives-framework. Two alternative architectures compliant with Open Access concepts are presented: OAI-PMH and Web Services via SOAP.A detailed comparison of both architectures is followed by the implementation of a prototype. This is based on a suitable technology for fullfilling the requirements of Open Access and contributes to the solution of the problems of the existing system. In the conclusion future developments are discussed

Handle System - Eine Architektur für eindeutige Bezeichner

Grundlagen zum Handle System, ein Überblick über Architektur und Methoden und dessen produktive Anwendung am AWI in Verbindung mit dem Publikationssystem ePI

BizWeb: Kreuzfahrtbuchungen mit Web Services - Projektdokumentation

Das Anwendungsziel war, mit Hilfe von Web Services, eine Kreuzfahrtbuchung in einem SAPSystem zu realisieren. Damit soll die Abfrage nach buchbaren Kreuzfahrten, die Buchung von Kreuzfahrten usw. in einem fiktiven Kreuzfahrtbuchungssystem über ein SAPSystem ermöglicht werden. Hierzu war eine Schnittstelle auf der Basis des Java Connectors zu realisieren. Dazu waren vielfältige Vorarbeiten notwendig, wie: ein Kreuzfahrtbuchungssystem im SAPSystem zu realisieren, das notwendige Datenmodell zu entwickeln, etc

GNA11 and N-RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system

Aim: Primary melanocytic tumours are uncommon neoplasms of the central nervous system. Although similarities with uveal melanomas have been hypothesized, data on their molecular features are limited. Methods: In this study, we investigated the mutational status of BRAF (V600E) , KIT, GNAQ, GNA11, N-RAS and H-RAS in a series of 19 primary melanocytic tumours of the CNS. Results: We identified six cases harbouring mutations in the hotspot codon 209 of the GNAQ gene and two cases with mutations in the hotspot codon 209 of the GNA11 gene. Two mutations in codon 61 of N-RAS were also found. In the SSCP analysis, no shifts corresponding to BRAF(V600E) mutations or suggesting activating mutations in the KIT gene were observed. Conclusions: In primary melanocytic tumours of the CNS, GNA11 and N-RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations. On the other hand, BRAF(V600E) mutations and activating KIT mutations seem to be absent or very rare in these tumours. \ua9 2012 The Authors. Neuropathology and Applied Neurobiology \ua9 2012 British Neuropathological Society