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 diffus e 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 commo nly deleted region mapping to 6q21-q22, The most frequent gains involved ch romosome arms 12q (63%), 18q and 22q (37% each), as well as 1q, 9q, 11q, 12 p, 16p and 17q (26% each), High-level amplifications were mapped to 9p23-p2 4 (1 tumor) and to 18q21-q23 (2 tumors). However, PCR-based analysis, South ern blot analysis and high-resolution matrix-CGH of the BCL2 gene revealed neither evidence for amplification nor for genetic rearrangement. Mutationa l analysis of BCL10 in 16 PCNSL identified four distinct sequence polymorph isms but no mutation,Taken together, our data do not support a role of BCL2 rearrangement/amplification and BCL10 mutation in PCNSL but indicate a num ber of novel chromosomal regions that likely carry yet unknown tumor suppre ssor genes or proto-oncogenes involved in the pathogenesis of these tumors.