Publication

Expression patterns of cell cycle components in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors

Agesen, T. H., Florenes, V. A., Molenaar, W. M., Lind, G. E., Berner, J-M., Plaat, B. E. C., Komdeur, R., Myklebost, O., van den Berg, E. & Lothe, R. A., Jan-2005, In : Journal of neuropathology and experimental neurology. 64, 1, p. 74-81 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

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(KIP1) 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.

Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalJournal of neuropathology and experimental neurology
Volume64
Issue number1
Publication statusPublished - Jan-2005

    Keywords

  • cell cycle, malignant peripheral nerve sheath tumors, neurofibromatosis, NF1, p16(INK4A), western blot, SOFT-TISSUE SARCOMAS, COMPARATIVE GENOMIC HYBRIDIZATION, KINASE CDK 2, VONRECKLINGHAUSEN NEUROFIBROMATOSIS, SUPPRESSOR GENE, HUMAN CANCER, P53 PROTEIN, TP53, MUTATIONS, MDM2

ID: 4301105