CHARACTERISTIC PATTERN OF CHROMOSOMAL GAINS AND LOSSES IN MARGINAL ZONE B-CELL LYMPHOMA DETECTED BY COMPARATIVE GENOMIC HYBRIDIZATION

Marginal zone B cell lymphoma (MZBCL) represents a distinct subtype of B cell non-Hodgkin's lymphoma, which has been recently recognized and defined as a disease entity. We investigated 25 cases (18 at primary diagnosis and seven during the course of disease) of MZBCL by comparat ive genomic hybridization (CGH) and compared these results with cytoge netic, fluorescence in situ hybridization (FISH), and Southern blot da ta. Twenty of the 25 cases (80%) showed gains (total 49) or losses (to tal 15) of genetic material. In extranodal, nodal, and splenic MZBCL, material of chromosomes 3 (52% of cases), 18 (32%), X (24%), and 1q (1 6%) was most frequently gained, whereas losses predominantly involved chromosomes 17 (16%) and 9 (12%). High-level amplifications involving the regions 18q21-23 and 18q21-22, respectively, were detected in two cases. Gains of chromosomes 1q and 8q and losses of chromosome 17 or 1 7p occurred more frequently in relapsed or progressive lymphomas. For all of the frequently affected chromosomes, CGH allowed narrowing of t he relevant subregions including 3q21-23, 3q25-29 and 18q21-23. By Sou thern blot analysis, the BCL2, BCL6, and CMYC proto-oncogenes were fou nd to be a part of the over-represented regions in two cases, one case , and two cases, respectively, with gains involving 18q, 3q or 8q. In 13 cases, CGH revealed chromosomal imbalances which were not detected by cytogenetic analysis but could be confirmed by FISH or Southern blo t analysis in all cases investigated. On the other hand, CGH failed to detect trisomy 3, trisomy 18, and deletion 7q in three cases with a r ow proportion of tumor cells bearing these abnormalities, as shown by interphase FISH. The characteristic pattern of chromosomal gains and l osses detected in this study confirms the distinct nature of MZBCL and may point to chromosomal regions involved in the pathogenesis of thes e neoplasms.