Chromosomal imbalances in primary lymphomas of the central nervous system

Abstract

Twenty-two primary central nervous system lymphomas of immunocompetent adults were studied by comparative genomic hybridization. All were high-grade diffuse large B cell lymphomas. Comparative genomic hybridization revealed an average of 5.5 chromosomal changes per tumor, with gains being more common than losses (3.5 vs. 2.0). The most frequent DNA copy number changes were gains on chromosomes 1, 12, 18 (41% each), 7 (23%), and 11 (18%) and losses involving chromosomes 6 (59%), 18, and 20 (18% each). Commonly involved regions were +12q (41%), +18q (36%), +1q (32%), and +7q (23%), as well as -6q (50%), -6p (18%), -17p, and -18p (14% each). High-level gains were found on 7 chromosomes, mainly involving chromosomes 18q (23%), 12q (18%), and 1q (14%). Minimal common regions of over- and underrepresentation were found on +1q25-31, -6q16-21, +7q11.2, +12p11.2-13, +12q12-14, +12q22-24.1, and +18q12.2-21.3. A significant correlation between loss of DNA copy numbers on chromosome 6q and shorter survival could be established (10.2 vs. 22.3 months; P < 0.05). Our findings suggest that chromosomal imbalances of primary central nervous system lymphomas are similar to those of diffuse large B cell lymphomas at other locations and are probably not related to cerebral presentation; however, they may be prognostically relevant.

Figure 1.

Summary of gains and losses of DNA sequences identified by CGH. Gains are shown as black bars on the right side of the chromosome ideogram and losses on the left. High-level amplifications are marked as white inlays within the black bars. Each vertical represents the affected chromosomal region seen in a single tumor specimen in case number order.

Figure 2.

Two-color CGH image of hybridized chromosomes of case 15 with computer-generated CGH ratio superimposed. Green regions represent gains, red regions losses (top). Calculated CGH profile shows gains on 1q, 7q, 13q, and 18q as well as losses on 2p, 6q, und 18p. Average ratio profile of autosomal chromosomes is depicted with a 95% confidence interval. The ratios are plotted alongside the chromosome ideogram. A balanced copy number has a baseline ratio of 1, represented by the central black line; thresholds of copy number gains (1.25) and losses (0.75) are shown (bottom).