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quinta-feira, 20 de outubro de 2011

NATURE | LETTER

The role of dyking and fault control in the rapid onset of eruption at Chaitén volcano, Chile

Nature

478,

374–377

(20 October 2011)

doi:10.1038/nature10541

Received: 12 March 2011
Accepted: 30 August 2011
Published online: 19 October 2011

Rhyolite is the most viscous of liquid magmas, so it was surprising that on 2 May 2008 at Chaitén Volcano, located in Chile’s southern Andean volcanic zone, rhyolitic magma migrated from more than 5 km depth in less than 4 hours (ref. 1) and erupted explosively with only two days of detected precursory seismic activity². The last major rhyolite eruption before that at Chaitén was the largest volcanic eruption in the twentieth century, at Novarupta volcano, Alaska, in 1912. Because of the historically rare and explosive nature of rhyolite eruptions and because of the surprisingly short warning before the eruption of the Chaitén volcano, any information about the workings of the magmatic system at Chaitén, and rhyolitic systems in general, is important from both the scientific and hazard perspectives. Here we present surface deformation data related to the Chaitén eruption based on radar interferometry observations from the Japan Aerospace Exploration Agency (JAXA) DAICHI (ALOS) satellite. The data on this explosive rhyolite eruption indicate that the rapid ascent of rhyolite occurred through dyking and that melt segregation and magma storage were controlled by existing faults.

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NATURE | LETTER

A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

Nature

(2011)

doi:10.1038/nature10539

Received: 01 February 2011
Accepted: 02 September 2011
Published online: 19 October 2011

So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes¹; risk factors associated with RCC include smoking, obesity and hypertension². A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers³. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene⁴; it also stimulates the transcription of hypoxia inducible factor⁵ (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes⁶. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.