Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Cultivation and fishing. Arnager fishing village, a common-field system on Bornholm?

På det sydvestlige Bornholm ligger fiskerlejet Arnager, der i litteraturen ikke har været skænket megen opmærksomhed, men som på original-1-kortet giver indtryk af at være et dyrkningsfællesskab. Dyrkningsfællesskaber er ellers ukendte på Bornholm, som derved skiller sig markant ud fra resten af Danmark i sin bebyggelsesstruktur. Denne artikel undersøger, hvorvidt fiskerlejet kan betragtes som et dyrkningsfællesskab med udgangspunkt i original-1-kortet og diverse skriftlige kilder. Undersøgelsen er således også et eksempel på, hvor meget information, der kan trækkes ud af original-1-kortet som kilde, når dette sammenholdes med både yngre og ældre kortkilder. I undersøgelsen inddrages områdets bonitet og stednavnestof, og der redegøres for den lokale anvendelse af betegnelsen ’stæl’, der er essentiel for forståelsen af jord-delingen i fiskerlejets vang.In the southwestern part of the Danish island of Bornholm we find a small fishing community called Arnager. The arable fields belonging to fishing communities of this type were usually not organized in an open field system (Danish dyrkningsfællesskab), with an arrangement of scattered land strips communally regulated but privately owned – least of all on Bornholm where no such systems are known to have existed, not even in arable-dominated villages. Nevertheless, Arnager appears like a regular open-field-system community on the first cadastral map, known as the 'original-1-map'. In order to investigate whether Arnager can be characterized as a village with an open field system or not, the information drawn from the original-1-map is compared to information from other maps available such as modern LiDAR maps as well as written sources. Furthermore, the quality of the soil and the local place names are taken into consideration in order to assess whether Arnager can in fact be seen as having been a fishing community with an open field system. An examination of the abovementioned sources concludes that a community of shared resources did in fact exist in Arnager in the 19th century, but clear evidence is lacking in respect to judge whether Arnager can be seen as a regular open field system as known from the rest of Denmark further back in time

Biologisk undersökning av grunda havsvikar: effekter av fintrådiga alger och skörd

Biologisk undersökning av grunda havsvikar: effekter av fintrådiga alger och skördRegionala inventeringsrapporter import från MDP 2015-05</p