Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001).
Of the five target genes that were enriched in the glioblastoma pathway, in the WikiPathway database, both HRas proto-oncogene, GTPase and MET proto-oncogene, receptor tyrosine kinase target genes of hsa-miR-139-5p, were found to be significantly associated with patient survival.
In this study, we found that expression of the MET oncogene was associated with neurospheres expressing the gene signature of mesenchymal and proneural subtypes of glioblastoma.
MET gain was detected in primary glioblastomas (47%) and secondary glioblastomas (44%), suggesting that this genetic alteration plays a role in the pathogenesis of both glioblastoma subtypes.
Rapid radiographic and clinical improvement after treatment of a MET-amplified recurrent glioblastoma with a mesenchymal-epithelial transition inhibitor.
This phenomenon is especially common among tumors with PDGFRA amplification: overall, 43% of PDGFRA-amplified GBM were found to have amplification of EGFR or the hepatocyte growth factor receptor gene (MET) as well.
MET and its ligand hepatocyte growth factor (HGF) play a critical role in the proliferation, survival, migration, invasion, angiogenesis, stem cell characteristics, and therapeutic resistance and recurrence of glioblastomas.
In contrast to the classical subtype of primary glioblastoma, the cases studied here were characterized by the absence of EGFR amplification, PTEN loss, and 9p homozygous deletion and overexpression of p53, PDGFRα, and c-MET, suggesting that they can be classified as the proneural or mesenchymal subtype of glioblastoma and benefit from intensive therapy that includes temozolomide.
This translational correlative component to the MET-PET clinical trials can lead to a better understanding of the existing controversies and can enhance our knowledge for future randomization of GBM patients based on their tumor gene signatures to achieve better prognosis and treatment outcome.
Intravenous administration of this formulation enhanced the curative efficacy of TMZ by downregulating the hepatocyte growth factor receptor (c-MET) gene in GBM U87 cells.
PV-O glioblastomas were associated with lower expression of VEGFC (p = 0.032) than other periventricular locations, whereas MET overexpression remained exceptional.
Although the extent of the amplified domain varied, the close vicinity of the MET gene was the only region consistently amplified in these glioblastomas.
We investigated the effect of HGF/SF on matrix metalloproteinase-2 (MMP-2), membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitors of metalloproteinases (TIMPs), expressions of c-Met/HGF receptor-positive human glioblastoma cells.
We investigated the molecular factors and pathway activation signatures that determine sensitivity to c-MET inhibitors in a panel of glioblastoma and medulloblastoma cells, glioblastoma stem cells, and established cell line-derived xenografts using functional assays, reverse protein microarrays, and in vivo tumor volume measurements, but validation with animal survival analyses remains to be done.