|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
All or any of three exons of the p16 gene were homozygously delted in 11 (35.5%) of 31 glioblastomas, none of 9 anaplastic astrocytomas and 5 astrocytomas, and in all 6 human glioma cell lines.
|
7497469 |
1995 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
After controlling for the contamination of tumor samples with normal cells, homozygous loss of MTS1 was found in 13 of 25 anaplastic astrocytomas (WHO grade III) and in 27 of 46 cases of glioblastomas (WHO grade IV) but in none of seven astrocytomas (WHO grade II).
|
7805033 |
1995 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Amplification of the CDK4 gene was present in 7 of 14 (50%) glioblastomas and 3 of 11 (27%) anaplastic astrocytomas with no losses at the CDKN2 locus as well as in 2 of 32 (6%) glioblastomas with CDKN2 losses.
|
7987821 |
1994 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
These data suggest that the target of deletion in glioblastoma multiforme includes both p15 and p16 genes.
|
7987828 |
1994 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
As a whole, the data assign a tumor suppressor role to p15 and confirm homozygous deletions as the favorite mechanism for the inactivation of MTS1 and MTS2 in glioblastomas.
|
8526910 |
1995 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated.
|
8548755 |
1996 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The presence of p16 gene mutations only in glioblastomas suggests that they are late events in glioma development.
|
8552400 |
1996 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In the glioblastomas with no alterations of CDKN2A, CDK4 or RB1, several other genes (CCND1, CCND2, CCND3, CDK6, E2F, CDK7, MYC and MYCN) whose products take part in cell cycle regulation were examined.No abnormalities were detected.
|
8806696 |
1996 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In contrast, 7/13 glioblastomas with hemizygous deletions of CDKN2A and 8/11 glioblastomas with hemizygous deletions of CDKN2B showed no or weak expression.
|
9000591 |
1997 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Loss of p16 expression was detected in 11/18 (61%) glioblastomas.
|
9210874 |
1997 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme.
|
9217972 |
1997 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all.
|
9284834 |
1997 |
|
Glioblastoma
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
Hypermethylation of CpG islands in the 5' region of the p16 gene was identified in only 1 case, suggesting that this alternative mechanism of gene silencing is rarely responsible for loss of p16 expression in glioblastomas.
|
9334810 |
1997 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
However, p16 deletions were significantly more frequent in the former (10/28; 36%) than in the latter (1/23, 4%; P = 0.0075), suggesting that this alteration constitutes an additional genetic hallmark of the primary (de novo) glioblastoma.
|
9341929 |
1997 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Five of 25 (20%) glioblastomas had diffuse p16 immunohistochemical positivity.
|
9600204 |
1998 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In astrocytomas low CDKN2/p16 expression was associated with high histologic malignancy grade (p = 0.002): CDKN2/p16 protein level was decreased in 9 out of 10 glioblastomas, in 5 out of 9 anaplastic astrocytomas, in 3 out of 10 grade II astrocytomas and in none of pilocytic astocytomas (0/7).
|
10359140 |
1999 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The human glioblastoma cell line U87MG was doubly transfected with the plasmids pVgRXR and pIND harboring the wild-type p16 gene.
|
10360478 |
1999 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Including 20 additional glioblastoma-derived cell lines we detected that in 19 of the total 31 lines at least one exon was lost bringing the rate of p16 loss in the whole panel to 61%.
|
10536182 |
1999 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We have also shown the presence of heterogeneous cell populations within the glioblastoma masses based on the variety of the mutated p16 sequences.
|
10536183 |
1999 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results strongly support the concept that p16INK4a is involved in the regulation of proliferation in glioblastomas.
|
10564531 |
1999 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Loss of the p16INK4a gene on 9p21 has been documented in a wide range of human tumors, including one third of glioblastomas.
|
10665922 |
2000 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Seventy-six percent of GBs (103 of 136), 72% of AAs (28 of 39), and 67% of As (10 of 15) had deregulated p53 pathway either by mutation of TP53, amplification of MDM2, or homozygous deletion/mutation of p14ARF.
|
10667596 |
2000 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
RT-2 rat GBM cell line was used to investigate if the p16 gene induces dominant suppression of glioblastoma growth.
|
10720483 |
2000 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Neither p53 expression nor p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival. p16 immunostaining was negative in 16% of AAs and in 44% of GBs, and it correlated inversely with survival in both uni- and multivariate analyses. pRb immunostaining was negative only in 8% of both AAs and GBs and the absence of p16 and pRb were mutually exclusive.
|
10896207 |
2000 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The genes encoding the cyclin-dependent kinase inhibitors p16INK4A (CDKN2A) and p15INK4B (CDKN2B) are frequently homozygously deleted in a variety of tumor cell lines and primary tumors, including glioblastomas in which 40-50% of primary tumors display homozygous deletions of these two loci.
|
10939591 |
2000 |