Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Wiesner, T; Obenauf, AC; Cota, C; Fried, I; Speicher, MR; Cerroni, L.
Alterations of the cell-cycle inhibitors p27(KIP1) and p16(INK4a) are frequent in blastic plasmacytoid dendritic cell neoplasms.
J Invest Dermatol. 2010; 130(4):1152-1157
Doi: 10.1038/jid.2009.369
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- Leading authors Med Uni Graz
- Cerroni Lorenzo
- Obenauf Anna Christina
- Wiesner Thomas
- Co-authors Med Uni Graz
- Fried Isabella
- Speicher Michael
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- Abstract:
- Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive malignancy with a median survival of 12-14 months. To identify pathogenetic relevant genomic aberrations and molecular targets for therapy, we analyzed skin biopsy samples obtained from 14 patients using high-resolution array-based comparative genomic hybridization and immunostaining. Losses of chromosomes 9, 12, 13, and 15 were detected most frequently. Loss of the CDKN1B locus was the most common finding and was detected in 64% of tumors. In all but one case, the dose-dependent haploinsufficient cell-cycle inhibitor p27(KIP1), encoded by CDKN1B, was weakly expressed in the nuclei of tumor cells. Losses of the CDKN2A-ARF-CDKN2B locus occurred in 50% of patients, and in one case a distinct biallelic loss was identified. The cell-cycle inhibitor p16(INK4a), which is encoded by CDKN2A, was not expressed in tumor cells, suggesting a complete loss of function. Loss of chromosome 13, including the RB1 gene, was observed in 43% of tumors. These results imply that alterations of the cell-cycle checkpoint controlling proteins p27(KIP1), p16(INK4a), and RB1 may exert a profound effect in malignant transformation in BPDCN. The elucidation of the affected pathways may guide the development of new treatments specifically designed for this aggressive disease entity.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
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- Chromosome Aberrations -
- Comparative Genomic Hybridization -
- Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - metabolism
- Cyclin-Dependent Kinase Inhibitor p27 -
- Dendritic Cells - pathology Dendritic Cells - physiology
- Female -
- Gene Dosage -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism
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- Skin Neoplasms - pathology Skin Neoplasms - physiopathology