title: Chromosomal imbalances and partial uniparental disomies in primary central nervous system lymphoma.
abstract: To determine the pattern of genetic alterations in primary central nervous system lymphomas (PCNSL), 19 PCNSL were studied by high-density single-nucleotide polymorphism arrays. Recurrent losses involved 6p21.32, 6q21, 8q12-12.2, 9p21.3, 3p14.2, 4q35.2, 10q23.21 and 12p13.2, whereas gains involved 18q21-23, 19q13.31, 19q13.43 and the entire chromosomes X and 12. Partial uniparental disomies (pUPDs) were identified in 6p and 9p21.3. These genomic alterations affected the HLA locus, the CDKN2A/p16, CDKN2B/p15 and MTAP, as well as the PRDM1, FAS, MALT1, and BCL2 genes. Increased methylation values of the CDKN2A/p16 promoter region were detected in 75% (6/8) PCNSL. Gene expression profiling showed 4/21 (20%) minimal common regions of imbalances to be associated with a differential mRNA expression affecting the FAS, STAT6, CD27, ARHGEF6 and SEPT6 genes. Collectively, this study unraveled novel genomic imbalances and pUPD with a high resolution in PCNSL and identified target genes of potential relevance in the pathogenesis of this lymphoma entity.
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne D-50924, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schwindt
authors.forename: I
authors.initials: I
authors.lastname: Vater
authors.forename: M
authors.initials: M
authors.lastname: Kreuz
authors.forename: M
authors.initials: M
authors.lastname: Montesinos-Rongen
authors.forename: A
authors.initials: A
authors.lastname: Brunn
authors.forename: J
authors.initials: J
authors.lastname: Richter
authors.forename: S
authors.initials: S
authors.lastname: Gesk
authors.forename: O
authors.initials: O
authors.lastname: Ammerpohl
authors.forename: O D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: D
authors.initials: D
authors.lastname: Hasenclever
authors.forename: M
authors.initials: M
authors.lastname: Deckert
authors.forename: R
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D024182:Uniparental Disomy
chemical_list: D014408:Biomarkers, Tumor