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RESEARCH PRODUCT
Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma
Juan SandovalJose Antonio López-guerreroDavid Hervás-marínOnofre SanmartínInma QuilisM. Carmen BañóJ. Carlos IgualFaatiemah Higginssubject
0301 basic medicineEpigenomicsMaleSkin NeoplasmsDiseaseBiochemistryActinic KeratosisGenomeEpigenesis Genetic0302 clinical medicineRisk FactorsMedicine and Health SciencesSkin TumorsAged 80 and overMultidisciplinaryDNA methylationQRSquamous Cell CarcinomasMethylationMiddle AgedPrognosisChromatinNucleic acidsGene Expression Regulation NeoplasticKeratosis ActinicOncology030220 oncology & carcinogenesisDNA methylationCarcinoma Squamous CellDisease ProgressionMedicineEpigeneticsFemaleDNA modificationChromatin modificationResearch ArticleChromosome biologyCell biologyCutaneous squamous cell carcinomaKeratosisScienceDermatologyBiologyCarcinomas03 medical and health sciencesDiagnostic MedicineCarcinomaGeneticsCancer Detection and DiagnosismedicineHumansEpigeneticsAgedNeoplasm StagingTreatment GuidelinesHealth Care PolicyBiology and life sciencesActinic keratosisCancers and NeoplasmsDNAmedicine.diseaseDNA FingerprintingDna methylation profilingHealth Care030104 developmental biologyCancer researchGene expressionNeoplasm Recurrence LocalSkin cancerGenome-Wide Association Studydescription
ABSTRACTCutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates between stages. Importantly, a direct comparison of low-risk and high-risk stages revealed epigenetic traits characteristic of high-risk tumours. Finally, a prognostic prediction model in cSCC patients identified a methylation signature able to predict the overall survival of patients. Thus, the analysis of DNA-methylation in cSCC revealed changes during the evolution of the disease through the different stages that can be of great value not only in the diagnosis but also in the prognosis of the disease.
year | journal | country | edition | language |
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2019-09-20 |