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Expression patterns of cell cycle components in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors
- Source :
- University of Groningen, Journal of neuropathology and experimental neurology, 64(1), 74-81. Oxford University Press
- Publication Year :
- 2005
-
Abstract
- The molecular biology underlying the development of highly malignant peripheral nerve sheath tumors (MPNSTs) remains mostly unknown. In the present study, the expression pattern of 10 selected cell cycle components is investigated in a series of 15 MPNSTs from patients with (n = 9) or without (n = 5) neurofibromatosis type 1 (NF1). Thirteen tumors did not express the cyclin-dependent kinase inhibitor, p16(INK4A), an observation that was related to homozygote gene deletions in three tumors, heterozygote deletions in five, and gross gene rearrangements in five. The absence of protein expression in the tumors with one seemingly intact allele was not caused by promoter hypermethylation of p16(INK4A) or p14(ARF). All tumor samples expressed normal sized RB1, cyclin D3, CDK2, CDK4, p21(CIP1), and p27(KlP1) proteins, and only a single tumor showed an aberrant protein band for one of these proteins, p21(CIP1). Cyclin D1 was absent in four tumors; all except one tumor showed expression of TP53 protein, and three of nine MPNSTs had expression of normal-sized MDM2. In conclusion, this study shows that the vast majority of MPNSTs had gross rearrangements of the p16(INK4A) gene, explaining the absence of the encoded protein in the same tumors. The level of expression was equally distributed between the familial (NF1) and sporadic cases, although it should be noted that the 2 cases with p16(INK4A) expression were sporadic. The data imply that the complete absence of p16(INK4A) is sufficient for activation of the cell cycle in most MPNSTs; thus, it is not necessary for tumor proliferation to further stimulate the cycle through alteration of other central components.
- Subjects :
- Male
Pathology
P53 PROTEIN
Cell Cycle Proteins
Retinoblastoma Protein
Nerve Sheath Neoplasms
SOFT-TISSUE SARCOMAS
COMPARATIVE GENOMIC HYBRIDIZATION
TP53
p16(INK4A)
General Medicine
Middle Aged
Cell cycle
Gene Expression Regulation, Neoplastic
Neurology
KINASE CDK 2
Female
cell cycle
Adult
medicine.medical_specialty
Neurofibromatosis 1
VONRECKLINGHAUSEN NEUROFIBROMATOSIS
Blotting, Western
Biology
Pathology and Forensic Medicine
Cellular and Molecular Neuroscience
Cyclin D1
MDM2
medicine
Humans
Neurofibromatosis
Cyclin D3
neoplasms
Cyclin-Dependent Kinase Inhibitor p16
Aged
Neurofibromatoses
neurofibromatosis
western blot
HUMAN CANCER
Cyclin-dependent kinase 4
MUTATIONS
Cyclin-dependent kinase 2
Heterozygote advantage
medicine.disease
NF1
Cancer research
biology.protein
malignant peripheral nerve sheath tumors
Neurology (clinical)
Tumor Suppressor Protein p53
SUPPRESSOR GENE
Subjects
Details
- Language :
- English
- ISSN :
- 00223069
- Volume :
- 64
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of neuropathology and experimental neurology
- Accession number :
- edsair.doi.dedup.....b6c484521c2aae4ec4202380dcf416b8