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001-es BibID:BIBFORM068928
Első szerző:Murnyák Balázs (molekuláris biológus, genetikus)
Cím:PARP1 expression and its correlation with survival is tumour molecular subtype dependent in glioblastoma / Balázs Murnyák, Mahan C. Kouhsari, Rotem Hershkovitch, Bernadette Kálmán, György Marko-Varga, Álmos Klekner, Tibor Hortobágyi
Dátum:2017
ISSN:1949-2553
Megjegyzések:Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1's expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1's associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of Proneural and Classical GBM subtypes. Additionally, higher 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 expression and PARP1 protein level correlated with ATRX loss and p53 overexpression. Furthermore, higher PARP1 expression together with wildtype TP53 indicated shorter survival (p=0.039). Therefore, due to subtype specificity, PARP1 expression level and TP53 mutation status are reliable marker candidates to distinguish Proneural and Classical subtypes, with prognostic and therapeutic implications in GBM.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
glioma
glioblastoma
p53
PARP1
Megjelenés:Oncotarget. - 8 : 28 (2017), p. 46348-46362. -
További szerzők:Kouhsari, Mahan C. Hershkovitch, Rotem Kálmán Bernadette Marko-Varga György Klekner Álmos (1970-) (idegsebész) Hortobágyi Tibor (1965-) (patológus)
Pályázati támogatás:ÚNKP-16-3
Egyéb
KTIA_13_NAP-A-II/7
Egyéb
KTIA_13_NAP-A-V/3
Egyéb
AGR_PIAC_13-1-2013-0008
Egyéb
GINOP-2.3.2-15-2016-00043
GINOP
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
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2.

001-es BibID:BIBFORM065513
Első szerző:Murnyák Balázs (molekuláris biológus, genetikus)
Cím:Immunohistochemical correlates of TP53 somatic mutations in cancer / Balázs Murnyák, Tibor Hortobágyi
Dátum:2016
ISSN:1949-2553
Megjegyzések:Despite controversy on the correlation between p53 accumulation and TP53 mutational status, immunohistochemical (IHC) detection of overexpressed protein has long been used as a surrogate method for mutation analysis. The aim of our study was to characterise the IHC expression features of TP53 somatic mutations and define their occurrence in human cancers. A large-scale database analysis was conducted in the IARC TP53 Database (R17); 7878 mutations with IHC features were retrieved representing 60 distinct tumour sites. The majority of the alterations were immunopositive (p<0.001). Sex was known for 4897 mutations showing a female dominance (57.2%) and females carrying negative mutations were significantly younger. TP53 mutations were divided into three IHC groups according to mutation frequency and IHC positivity. Each group had female dominance. Among the IHC groups, significant correlations were observed with age at diagnosis in breast, bladder, liver, haematopoietic system and head & neck cancers. An increased likelihood of false negative IHC associated with rare nonsense mutations was observed in certain tumour sites. Our study demonstrates that p53 immunopositivity largely correlates with TP53 mutational status but that expression is absent in certain mutation types. Besides, describing the complex IHC expression of TP53 somatic mutations, our results reveal some caveats for the diagnostic practice.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
IARC TP53 Database
Immunohistochemistry
TP53 mutations
cancer
p53
Megjelenés:Oncotarget 7 : 40 (2016), p. 64910-64920. -
További szerzők:Hortobágyi Tibor (1965-) (patológus)
Pályázati támogatás:KTIA_13_NAP-A-II/7
Egyéb
KTIA_13_NAP-A-V/3
Egyéb
AGR_PIAC_13-1-2013-0008
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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