Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma

Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression (‘SCNA-genes’) in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer

Responses of flowering phenology of snowbed plants to an experimentally imposed extreme advanced snowmelt

In snowbed habitats, characterized by a long-lasting snow cover, the timing of snowmelt can be included among the major factors controlling plant phenology. Nevertheless, only a few ecological studies have tested the responses of flowering phenology of species growing in very late snow-free habitats to an advanced snowmelt (AS) date. The aim of this study was to determine the impacts of an extremely earlier melt-out of snow on flowering phenology of vascular plant species inhabiting an alpine snowbed. The study was conducted in the high Gavia Valley (Italy, 2,700 m a.s.l.). On 30th May 2012, we removed manually the snow cover and set up an experiment with 5 AS and 5 control plots. Phenological observations of the most abundant vascular species were conducted every 4–6 days. Moreover, we calculated cumulative soil temperature and recorded the mortality of reproductive structures of three species. For several species flowering occurred earlier, and the prefloration period was extended in the AS treatment in comparison with the control. For the majority of species, cumulative soil temperatures in the AS treatment and the control were comparable, confirming that temperature exerts the main control on the flowering of the species inhabiting snowbeds. Earlier flowering species resulted more affected by an AS date in comparison with later flowering species. The mortality of reproductive structures did not increase in the AS treatments in comparison with the control suggesting that few and weak frost events in late spring do not affect the survival of reproductive structures of the species studied

Aalenian to Cenomanian Radiolaria of the Bermeja Complex (Puerto Rico) and Pacific origin of radiolarites on the Caribbean Plate

The study of the radiolarian ribbon chert is a key in determining the origins of associated Mesozoic oceanic terranes and may help to achieve a general agreement regarding the basic principles on the evolution of the Caribbean Plate. The Bermeja Complex of Puerto Rico, which contains serpentinized peridotite, altered basalt, amphibolite, and chert (Mariquita Chert Formation), is one of these crucial oceanic terranes. The radiolarian biochronology presented in this work is mainly based by correlation on the biozonations of Baumgartner et al. (1995) and O'Dogherty (1994) and indicates an early Middle Jurassic to early Late Cretaceous (late Bajocian-early Callovian to late early Albian-early middle Cenomanian) age. The illustrated assemblages contain about 120 species, of which one is new (Pantanellium karinae), and belonging to about 50 genera. A review of the previous radiolarian published works on the Mariquita Chert Formation and the results of this study suggest that this formation ranges in age from Middle Jurassic to early Late Cretaceous (late Aalenian to early-middle Cenomanian) and also reveal a possible feature of the Bermeja Complex, which is the younging of radiolarian cherts from north to south, evoking a polarity of accretion. On the basis of a currently exhaustive inventory of the radiolarite facies s.s. on the Caribbean Plate, a re-examination of the regional distribution of Middle Jurassic sediments associated with oceanic crust, and a paleoceanographic argumentation on the water currents, we come to the conclusion that the radiolarite and associated Mesozoic oceanic terranes of the Caribbean Plate are of Pacific origin. Eventually, a discussion on the origin of the cherts of the Mariquita Formation illustrated by Middle Jurassic to middle Cretaceous geodynamic models of the Pacific and Caribbean realms bring up the possibility that the rocks of the Bermeja Complex are remnants of two different oceans