Characteristic chromosomal imbalances in primary central nervous system lymphomas of the diffuse large B-cell type.
We performed a genome wide screening for genomic alterations on a series of 19 sporadic primary central nervous system lymphomas (PCNSL) of the diffuse large B-cell type by comparative genomic hybridization (CGH). The tumors were additionally analyzed for amplification and rearrangement of the BCL2 gene at 18q21 as well as for mutation of the recently cloned BCL10 gene at 1p22. Eighteen tumors showed genomic imbalances on CGH analysis. On average, 2.1 losses and 4.7 gains were detected per tumor. The chromosome arm most frequently affected by losses of genomic material was 6q (47%) with a commonly deleted region mapping to 6q21-q22. The most frequent gains involved chromosome arms 12q (63%), 18q and 22q (37% each), as well as 1q, 9q, 11q, 12p, 16p and 17q (26% each). High-level amplifications were mapped to 9p23-p24 (1 tumor) and to 18q21-q23 (2 tumors). However, PCR-based analysis, Southern blot analysis and high-resolution matrix-CGH of the BCL2 gene revealed neither evidence for amplification nor for genetic rearrangement. Mutational analysis of BCL10 in 16 PCNSL identified four distinct sequence polymorphisms but no mutation. Taken together, our data do not support a role of BCL2 rearrangement/amplification and BCL10 mutation in PCNSL but indicate a number of novel chromosomal regions that likely carry yet unknown tumor suppressor genes or proto-oncogenes involved in the pathogenesis of these tumors.
Weber
T
T
Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Weber
R G
RG
Kaulich
K
K
Actor
B
B
Meyer-Puttlitz
B
B
Lampel
S
S
Büschges
R
R
Weigel
R
R
Deckert-Schlüter
M
M
Schmiedek
P
P
Reifenberger
G
G
Lichter
P
P
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C090468:TP53BP2 protein, human