TY  - JOUR
A1  - Feldheim, Jonas
A1  - Kessler, Almuth F.
A1  - Monoranu, Camelia M.
A1  - Ernestus, Ralf-Ingo
A1  - Löhr, Mario
A1  - Hagemann, Carsten
T1  - Changes of O\(^6\)-Methylguanine DNA Methyltransferase (MGMT) promoter methylation in glioblastoma relapse—a meta-analysis type literature review
JF  - Cancers
N2  - Methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter has emerged as strong prognostic factor in the therapy of glioblastoma multiforme. It is associated with an improved response to chemotherapy with temozolomide and longer overall survival. MGMT promoter methylation has implications for the clinical course of patients. In recent years, there have been observations of patients changing their MGMT promoter methylation from primary tumor to relapse. Still, data on this topic are scarce. Studies often consist of only few patients and provide rather contrasting results, making it hard to draw a clear conclusion on clinical implications. Here, we summarize the previous publications on this topic, add new cases of changing MGMT status in relapse and finally combine all reports of more than ten patients in a statistical analysis based on the Wilson score interval. MGMT promoter methylation changes are seen in 115 of 476 analyzed patients (24%; CI: 0.21–0.28). We discuss potential reasons like technical issues, intratumoral heterogeneity and selective pressure of therapy. The clinical implications are still ambiguous and do not yet support a change in clinical practice. However, retesting MGMT methylation might be useful for future treatment decisions and we encourage clinical studies to address this topic
KW  - glioblastoma multiforme (GBM)
KW  - glioma
KW  - relapse
KW  - temozolomide
KW  - MGMT promoter methylation
KW  - therapy
KW  - resistance
KW  - recurrence
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193040
SN  - 2072-6694
VL  - 11
IS  - 12
ER  - 
TY  - JOUR
A1  - Feldheim, Jonas
A1  - Wend, David
A1  - Lauer, Mara J.
A1  - Monoranu, Camelia M.
A1  - Glas, Martin
A1  - Kleinschnitz, Christoph
A1  - Ernestus, Ralf-Ingo
A1  - Braunger, Barbara M.
A1  - Meybohm, Patrick
A1  - Hagemann, Carsten
A1  - Burek, Malgorzata
T1  - Protocadherin Gamma C3 (PCDHGC3) is strongly expressed in glioblastoma and its high expression is associated with longer progression-free survival of patients
JF  - International Journal of Molecular Sciences
N2  - Protocadherins (PCDHs) belong to the cadherin superfamily and represent the largest subgroup of calcium-dependent adhesion molecules. In the genome, most PCDHs are arranged in three clusters, α, β, and γ on chromosome 5q31. PCDHs are highly expressed in the central nervous system (CNS). Several PCDHs have tumor suppressor functions, but their individual role in primary brain tumors has not yet been elucidated. Here, we examined the mRNA expression of PCDHGC3, a member of the PCDHγ cluster, in non-cancerous brain tissue and in gliomas of different World Health Organization (WHO) grades and correlated it with the clinical data of the patients. We generated a PCDHGC3 knockout U343 cell line and examined its growth rate and migration in a wound healing assay. We showed that PCDHGC3 mRNA and protein were significantly overexpressed in glioma tissue compared to a non-cancerous brain specimen. This could be confirmed in glioma cell lines. High PCDHGC3 mRNA expression correlated with longer progression-free survival (PFS) in glioma patients. PCDHGC3 knockout in U343 resulted in a slower growth rate but a significantly faster migration rate in the wound healing assay and decreased the expression of several genes involved in WNT signaling. PCDHGC3 expression should therefore be further investigated as a PFS-marker in gliomas. However, more studies are needed to elucidate the molecular mechanisms underlying the PCDHGC3 effects.
KW  - glioblastoma multiforme
KW  - glioma
KW  - astrocytoma
KW  - recurrence
KW  - relapse
KW  - mRNA
KW  - protein
KW  - brain
KW  - expression
KW  - PCDHGC3
KW  - WNT signaling
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284433
SN  - 1422-0067
VL  - 23
IS  - 15
ER  -