|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These results indicate that the incidence of P16ink4 and CDK4 gene alterations in these two groups of tumors is different and suggest distinct pathogenetic etiologies may be associated with each neoplasm.
|
8847566 |
1996 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
All AFX and PDS investigated immunohistochemically presented with similar oncogene expression profiles (TP53, CCND1, CDK4 overexpression) and the single case with an AFX and PDS showed complete identical TP53 and PIK3CA mutation profiles in both tumors.
|
26943575 |
2016 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Alterations in the CDK4 region between codon 1 and codon 56 were not observed in any of the tumors.
|
9667525 |
1998 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The biological relevance of these interactions is underscored by observations that GRIM-19 promotes the inhibitory effect of CDKN2A on CDK4; and mutations from primary tumors disrupt its ability to interact with GRIM-19 and suppress E2F1-driven gene expression.
|
20522552 |
2010 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Furthermore, CDK4 variants are associated with obesity-associated tumors/cancer.
|
19634152 |
2009 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Putative tumour suppressor genes CDKN2A and CDKN2B (on chromosome 9p21) and CDKN2A-interacting cell growth regulatory genes CDK4 and Id-1 have been demonstrated to be involved in the pathogenesis of malignant melanoma (MM).
|
14646620 |
2003 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Besides the identification of well-recognized driver mutations of <i>BRAF</i> (3.1%), <i>RAS</i> family (6.2%), <i>NF1</i> (7.8%), and <i>KIT</i> (23.1%) in MMs, our study also found that (i) mutations and amplifications in the transmembrane nucleoporin gene <i>POM121</i> (30.8%) defined a patient subgroup with higher tumor proliferation rates; (ii) enrichment of structural variations between chromosomes 5 and 12 defined a patient subgroup with significantly worse clinical outcomes; (iii) over 50% of the MM patients harbored recurrent focal amplification of several oncogenes (<i>CDK4, MDM2,</i> and <i>AGAP2</i>) at 12q13-15, and this co-occurred significantly with amplification of <i>TERT</i> at 5p15, which was verified in the validation cohort; (iv) the PDX trial demonstrated robust antitumor effects of palbociclib in MMs harboring <i>CDK4</i> amplification.
|
30782616 |
2019 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Homozygous deletion of the CDKN2A gene was detected in 12 of 25 (48%) cases, CDK4 amplification in 4 of 25 (16%) tumors, and loss of heterozygosity at the RB gene in 8 of 22 (36%) informative cases.
|
9600204 |
1998 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Importantly, the combination of PI3K and CDK 4/6 inhibitors overcomes intrinsic and adaptive resistance leading to tumor regressions in PIK3CA mutant xenografts.
|
25002028 |
2014 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Ongoing studies include combinations of CDK4/6 inhibitors with endocrine therapy and phosphatidylinositol 3-kinase (PI3K) pathway inhibitors for hormone receptor-positive (HR+) breast cancers, and with selective RAF and MEK inhibitors for tumors with alterations in the mitogen activated protein kinase (MAPK) pathway such as melanoma.
|
27017286 |
2016 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Thus, whereas germ-line mutations of PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16(INK4A)/p14(ARF) tumor suppressor region may account for a subset of familial glioma cases.
|
10797439 |
2000 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Loss of the cyclin-dependent kinase 4-inhibitor (p16; MTS1) gene is frequent in and highly specific to lymphoid tumors in primary human hematopoietic malignancies.
|
7632963 |
1995 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Furthermore, the CDK4 mutant R24A weakly binds to PRMT5, inhibiting HCC cell cycle progression and tumor growth.
|
27708221 |
2016 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Subsequent Southern blot analysis of tumor DNA from the metastasis with the use of probes previously mapped to those regions indicated amplification of MYC at 8q23-24 and CDK4 and MDM2 at 12q13-15.
|
9723034 |
1998 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
These findings indicate that CDK4 and MDM2 gene alterations mainly occur in MCL with a wild-type INK4a/ARF locus and may contribute to the higher proliferation and more aggressive behavior of the tumors.
|
15781632 |
2005 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
: Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma.
|
10922411 |
2000 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
G-banding, comparative genomic hybridization (CGH), and real-time PCR for the MDM2 and CDK4 genes were performed to describe the genetic profile of this tumor and revealed aberrations that are common findings of parosteal osteosarcomas.
|
22749040 |
2012 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Real-time polymerase chain reaction failed to demonstrate the amplification of the murine double-minute type 2 gene and cyclin-dependent kinase 4 gene in this tumor.
|
16984623 |
2006 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
No tumor showed CDK4 gene mutation on single strand conformational polymorphism.
|
11311493 |
2001 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Tumors in group 1 had mutations in genes encoding proteins involved in a limited number of signal transduction cascades such as p16-cyclin D1/CDK4-RB or MDM2-p53-p21, where the aberration of one component seems to be sufficient to cause dysfunction of the cascade.
|
9685701 |
1998 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
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 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The most frequent copy number alterations identified were: amplification of the CDK4 oncogene (5 of 28; 17.9%) and deletion of the CDKN2A (4 of 28; 14.3%) and CDKN2B (3 of 28; 10.7%) tumor suppressor genes.
|
23979958 |
2013 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
We studied 38 cellular fibroadenomas and phyllodes tumors of various grade (World Health Organization benign, borderline, and malignant) with a panel of immunohistochemical stains (p53, CD117, phospho-Histone3, mdm2, cdk4) and screened 26 of the tumors for mutations across 30 cancer-related genes using PCR and mass-spectrometry based methods. p53 and phospho-Histone3 (mitotic marker) showed increased staining in higher grade phyllodes tumors.
|
21030860 |
2011 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Southern blot and/or differential PCR analyses identified amplification of PDGFRA (4q12), CCND3 (6p21), EGFR (7p12), CDK4 (12q14) and/or MDM2 (12q14.3-q15), and AKT1 (14q32.3) in the respective tumors.
|
12112531 |
2002 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In agreement with the in vitro data, homozygous Cdk4(R24C/R24C) mice developed tumors of various etiology within 8 to 10 months of their life span.
|
11756559 |
2002 |