20 research outputs found
Integrated genomic characterization of pancreatic ductal adenocarcinoma
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine
Asphalt volcanoes as a potential source of methane to late Pleistocene coastal waters
Every year, natural petroleum seepage emits 0.2-2 Tg of oil to the ocean. Significant oil seepage can build large underwater mounds, consisting of tar deposits with morphologies similar to volcanic lava flows, known as asphalt volcanoes. Such events are typically accompanied by large fluxes of the greenhouse gas methane. Marine sediments from the Santa Barbara basin, California, contain a record of elevated methane concentrations, anoxia and tar deposition during the Pleistocene epoch that had been attributed to dissolution of methane hydrates. However, the region is known to have exhibited oil seepage in the past. Here, we document the discovery of seven extinct asphalt volcanoes off the coast of southern California. The morphology of the deposits and geochemistry of samples taken from the two largest structures supports their classification as asphalt volcanoes, derived from a common source. We estimate that the two structures resulted from seepage of 0.07-0.4 Tg of oil, accompanied by the emission of 0.35-1.8 Tg of methane. Radiocarbon dating of carbonate deposits entrained with the asphalt indicates formation of the volcanoes between 44 and 31 kyr ago. The timing and volume of erupted hydrocarbons from the asphalt structures can explain some or all of the documented methane release and tar accumulation in the Santa Barbara basin during the Pleistocene. © 2010 Macmillan Publishers Limited