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Recurrent inactivation of the PRDM1 gene in primary central nervous system lymphoma

Courts, Cornelius
Montesinos-Rongen, Manuel
Brunn, Anna
Bug, Stefanie
Siemer, Dorte
Hans, Volkmar
Blumcke, Ingmar
Klapper, Wolfram
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Published in Journal of Neuropathology and Experimental Neurology. 2008, vol. 67, no. 7, p. 720-727
Abstract Primary lymphomas of the CNS (PCNSLs) show molecular features of the late germinal center exit B-cell phenotype and are impaired in their terminal differentiation as indicated by a lack of immunoglobulin class switching. Because the positive regulatory domain I protein with ZNF domain (PRDM1/BLIMP1) is a master regulator of terminal B-cell differentiation into plasma cells, we investigated a series of 21 PCNSLs for the presence of mutations in the PRDM1 gene and alterations in the expression pattern of the PRDM1 protein. Direct sequencing of all coding exons of the PRDM1 gene identified deleterious mutations associated with abrogation of PRDM1 protein expression in 4 of 21 (19%) PCNSLs. Thus, similar to systemic diffuse large B-cell lymphomas, PRDM1 may be a tumor suppressor in some PCNSL and contribute to lymphomagenesis by impairing terminal differentiation.
Keywords AdultAgedAged, 80 and overCentral Nervous System Neoplasms/*genetics/metabolism/pathologyDNA Mutational Analysis/methodsFemaleGene Expression Regulation, Neoplastic/*geneticsHumansLymphoma, B-Cell/*genetics/metabolism/pathologyMaleMiddle AgedRecurrenceRepressor Proteins/*genetics*Sequence Deletion
PMID: 18596541
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Research group Groupe Schaller Karl-Lothard (neurochirurgie) (851)
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COURTS, Cornelius et al. Recurrent inactivation of the PRDM1 gene in primary central nervous system lymphoma. In: Journal of Neuropathology and Experimental Neurology, 2008, vol. 67, n° 7, p. 720-727. doi: 10.1097/NEN.0b013e31817dd02d https://archive-ouverte.unige.ch/unige:19618

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Deposited on : 2012-04-23

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