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001-es BibID:	BIBFORM070807
Első szerző:	Murnyák Balázs (molekuláris biológus, genetikus)
Cím:	Genomic signature of PARP1 in glioblastoma subtypes / Balázs Murnyák, Mahan C. Kouhsari, Rotem Hershkovitch, Tibor Hortobágyi
Dátum:	2017
Megjegyzések:	Glioblastoma (GBM) is a highly aggressive and the most prevalent primary brain tumour in adults. Despite extensive efforts to improve treatment, GBM is still resistant to current postoperative therapies making GBM a compelling field of cancer research. Overexpression of PARP1 has been reported in various cancers, including GBM. Although PARP1 inhibition is a promising therapeutic target, no comprehensive analysis has addressed PARP1's expression regarding molecular heterogeneity in GBM. The main objective of our study was to evaluate PARP1's associations with GBM lineage specific markers, and its transcriptomic subtypes. PARP1's somatic mutations, copy number alterations (CNAs), and mRNA expression, as well as survival data were collected from the ♭Glioblastoma Multiforme' TCGA dataset. A bioinformatic analysis was conducted to evaluate PARP1's genetic signature and prognostic role in GBM. Our study revealed that PARP1 CNA gain and high mRNA expression levels are characteristics of Proneural and Classical GBM subtypes. Increased PARP1 levels exhibited an inverse correlation with patient survival (p<0.005) in the Classical subgroup. ATRX (p=0.006), and TP53 (p=0.015) mutations were associated with increased PARP1 mRNA expression. The observed subtype-specificity suggests that PARP1, together with p53, could be not only a diagnostic marker to differentiate Proneural and Classical subtypes, but also a predictive marker of shorter survival and poor therapy response in the Classical subgroup. Our study supports the therapeutic role of PARP inhibitors in GBM with the caveat that molecular heterogeneity needs to be taken into account.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok előadáskivonat PARP1 GBM Bioinformatics
Megjelenés:	Translational Bioinformatics : Abstract Book / Wellcome Genome Campus. - P18. p.
További szerzők:	Kouhsari, Mahan C. Hershkovitch, Rotem Hortobágyi Tibor (1965-) (patológus)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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