|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%).
|
9393738 |
1997 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In preliminary screens, mutations of PTEN were detected in 31% (13/42) of glioblastoma cell lines and xenografts, 100% (4/4) of prostate cancer cell lines, 6% (4/65) of breast cancer cell lines and xenografts, and 17% (3/18) of primary glioblastomas.
|
9072974 |
1997 |
|
Glioblastoma Multiforme
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Thus, PTEN appears to be the major target of inactivation on chromosome 10q in glioblastoma multiforme.
|
9331071 |
1997 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
One glioblastoma demonstrated evidence of homozygous deletion of PTEN by differential PCR analysis.
|
9426052 |
1998 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
These data do support a significant role for MMAC1 in GBM.
|
9499454 |
1998 |
|
Glioblastoma Multiforme
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Here, we show that PTEN expression potently suppressed the growth and tumorigenicity of human glioblastoma U87MG cells.
|
9860981 |
1998 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Infection of MMAC1-mutated U87MG glioblastoma cells with MMCB resulted in dose-dependent exogenous MMAC1 protein expression as detected by Western blotting of cell lysates.
|
9622068 |
1998 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Molecular analysis of two putative tumour suppressor genes, PTEN and DMBT, which have been implicated in glioblastoma multiforme disease progression.
|
9796706 |
1998 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
It has been shown in glioblastoma cell lines that loss of chromosome 10q, where the PTEN gene is located, is associated with increased angiogenic activity in the conditioned medium attributable to downregulation of thrombospondin-1, a negative regulator of angiogenesis.
|
10208463 |
1999 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Expression of carboxyl-terminal mutants in PTEN-deficient glioblastoma cells permitted the anchorage-independent growth of the cells that otherwise was suppressed by wild-type PTEN.
|
10468583 |
1999 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene.
|
11550308 |
1999 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Moreover, they suggest that PTEN alterations are equally involved in the 2 glioblastoma pathways defined by the presence of EGFR amplification and p53 mutation.
|
10096247 |
1999 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results support a model of molecular progression in gliomas in which the frequent deletion of 10q25-26 is an early event and is followed by the deletion of the MMAC/PTEN during the progression to high-grade GBMs.
|
9885980 |
1999 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here we report that recombinant adenovirus-mediated overexpression of MMAC1 in three different MMAC1-mutant glioblastoma cell lines blocked progression from G0/G1 to S phase of the cell cycle.
|
10344736 |
1999 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, loss of wild type PTEN represents one of the major abnormalities associated with astrocytic tumor progression to glioblastoma and provides a strong selective growth advantage when cultivating glioblastoma tissue in xenografts.
|
10560660 |
1999 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
PTEN/MMAC1 (phosphatase and tensin homolog/mutated in multiple advanced cancers 1) is a tumor suppressor gene, the inactivation of which is an important step in the progression of gliomas to end-stage glioblastoma multiforme.
|
11303623 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These findings indicate that the genetic or epigenentic inactivation of the hMLH1 gene is involved in a subset of early-onset gliomas and the PTEN1 gene could be a downstream target for mutation as observed in glioblastoma without MSI.
|
10734316 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
PTEN mutations have been implicated in the development of a variety of human neoplasia, including high-grade glioblastoma, prostate, breast, endometrial, and thyroid carcinoma.
|
10910075 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
For the GBMs with 'short-term' TTP vs. 'long-term' TTP, the studies revealed PTEN mutations in 4/21 vs. 2/21, TP53 mutations in 5/21 vs. 8/21, homozygous deletion of the CDKN2A gene in 5/21 vs. 6/21, overexpression of EGFR in 7/20 vs. 10/20, accumulation of p53 protein in 9/20 vs. 7/20 and of Mdm2 protein in 0/20 vs. 1/20 cases studied.
|
11083071 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Restoration of wild-type PTEN to glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes.
|
10691731 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
We previously demonstrated that MMAC1/PTEN has tumor suppressive properties in glioblastoma and prostate cancer.
|
11103942 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
PTEN mutation was observed in 8 of 64 tumors (12.5%), mainly GBMs (7 of 26, 26.9%), both with and without p53 mutation.
|
11051241 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Finally we found that SHIP-2, like PTEN, caused a potent cell cycle arrest in G(1) in glioblastoma cells, which is associated with an increase in the stability of expression of the cell cycle inhibitor p27(KIP1).
|
10958682 |
2000 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Excessive activity of the epidermal growth factor receptor and loss of the phosphatase PTEN are associated with glioblastoma, and both genes are required for normal growth and development.
|
11283316 |
2001 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
The LOH on markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was significantly associated with shorter survival in patients with GBM.
|
11596960 |
2001 |