6533b7d4fe1ef96bd12634cc
RESEARCH PRODUCT
Variation in genomic landscape of clear cell renal cell carcinoma across Europe
Christine CarreiraYasser RiazalhosseiniAlexander MazurSharon JacksonAlvis BrazmaLars EgevadSimon HeathIvana HolcatovaRosamonde E. BanksGraham ByrnesDoris LechnerJeremy SehmounLiliana GregerKonstantin G. SkryabinAnne Cambon-thomsenPierre LepageJon CartledgeDavid ZaridzeJohan RungMadeleine ArseneaultBehnoush Abedi-ardekaniEgor ProkhortchoukMarie NavratilovaAntoine DaunayMehran KarimzadehJiri ZavadilVictor RenaultEugenia S. BoulyginaDana MatesEmmanuel TubacherJuris ViksnaIvo GutHélène BlanchéMagdalena B. WozniakArtem V. ArtemovViorel JingaJörg TostNaveen S. VasudevPatricia HarndenMorag SeywrightAlexandre How-kitPaul BrennanGhislaine SceloLenka ForetovaG Mark LathropMarta GutEdgars CelmsMārtiņš OpmanisJing SuAnush MoukeriaMar Gonzàlez-portaMarie-therese BihoreauGuillaume BourqueAntonin BrisudaSergey M. RastorguevLouis LetourneauPeter SelbyAndris ZarinsMathieu BourgeyMario FoglioArtem V. Nedoluzhkosubject
AdultMaleOncogene Proteins FusionRNA SplicingGeneral Physics and AstronomyBiologymedicine.disease_causeGeneral Biochemistry Genetics and Molecular BiologyCohort StudiesTranscriptomePhosphatidylinositol 3-KinasesMutation RatemedicineHumansEpigeneticsCarcinoma Renal CellAgedAged 80 and overGeneticsFocal AdhesionsMutationMultidisciplinaryGenome HumanGene Expression ProfilingGenetic VariationGenomicsSequence Analysis DNAGeneral ChemistryMiddle Agedmedicine.diseaseHuman genetics3. Good healthEuropeGene Expression Regulation NeoplasticGene expression profilingClear cell renal cell carcinomaMutationFemaleCarcinogenesisClear cellSignal Transductiondescription
The incidence of renal cell carcinoma (RCC) is increasing worldwide, and its prevalence is particularly high in some parts of Central Europe. Here we undertake whole-genome and transcriptome sequencing of clear cell RCC (ccRCC), the most common form of the disease, in patients from four different European countries with contrasting disease incidence to explore the underlying genomic architecture of RCC. Our findings support previous reports on frequent aberrations in the epigenetic machinery and PI3K/mTOR signalling, and uncover novel pathways and genes affected by recurrent mutations and abnormal transcriptome patterns including focal adhesion, components of extracellular matrix (ECM) and genes encoding FAT cadherins. Furthermore, a large majority of patients from Romania have an unexpected high frequency of A:T>T:A transversions, consistent with exposure to aristolochic acid (AA). These results show that the processes underlying ccRCC tumorigenesis may vary in different populations and suggest that AA may be an important ccRCC carcinogen in Romania, a finding with major public health implications.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-10-29 | Nature Communications |