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- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 2. |
- Tornatore, Massimo, et al.
(författare)
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A Survey on Network Resiliency Methodologies against Weather-based Disruptions
- 2016
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Ingår i: PROCEEDINGS OF 2016 8TH INTERNATIONAL WORKSHOP ON RESILIENT NETWORKS DESIGN AND MODELING (RNDM). - : IEEE. - 9781467390231 ; , s. 23-34
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Konferensbidrag (refereegranskat)abstract
- Due to the increasing dependence on network services of our society, research has recently been concentrating on enhancing traditional protection strategies to withstand large-scale failures, as in case of disaster events. The recently-formed EU-funded RECODIS project aims at coordinating and fostering research collaboration in Europe on disaster resiliency in communication networks. In particular, the Working Group (WG) 2 of the RECODIS project focuses on developing new network resiliency strategies to survive weather-based disruptions. As a first step, WG2 members have conducted a comprehensive literature survey on existing studies on this topic. This paper classifies and summarizes the most relevant studies collected by WG2 members in this first phase of the project. While the majority of studies regarding weather-based disruptions deals with wireless network (as wireless channel is directly affected by weather conditions), in this survey we cover also disaster resiliency approaches designed for wired network if they leverage network reconfiguration based on disaster "alerts", considering that many weather-based disruptions grant an "alert" thanks to weather forecast.
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