Chromosomal alterations detected by comparative genomic hybridization in subgroups of gene expression-defined Burkitt's lymphoma.

ABSTRACT

BACKGROUND: Burkitt's lymphoma is an aggressive B-cell lymphoma characterized by typical morphological, immunophenotypic and molecular features. Gene expression profiling provided a molecular signature of Burkitt's lymphoma, but also demonstrated that a subset of aggressive B-cell lymphomas not fulfilling the current World Health Organization criteria for the diagnosis of Burkitt's lymphoma nonetheless show a molecular signature of Burkitt's lymphoma ('discrepant Burkitt's lymphoma'). Given the different treatment of Burkitt's lymphoma and diffuse large B-cell lymphomas we investigated molecular differences within gene expression-defined Burkitt's lymphoma. DESIGN AND METHODS: We studied tumors from 51 Burkitt's lymphoma patients, comprising 26 with classic Burkitt's lymphoma, 17 with atypical Burkitt's lymphoma and 8 with 'discrepant Burkitt's lymphoma', by comparative genomic hybridization and gene expression profiling. RESULTS: Classic and atypical Burkitt's lymphoma (excluding 'discrepant Burkitt's lymphoma'), in adult and pediatric cases do not differ in underlying genomic imbalances or gene expression suggesting that these subgroups are molecularly homogeneous. 'Discrepant Burkitt's lymphoma', however, differ dramatically in the absolute number of alterations from classic/atypical Burkitt's lymphoma and from diffuse large B-cell lymphoma. Moreover, this category includes lymphomas that carry both the t(14;18) and t(8;14) translocations and are clinically characterized by presentation in adult patients and an aggressive course. CONCLUSIONS: Pediatric and adult Burkitt's lymphoma are molecularly homogeneous, whereas 'discrepant Burkitt's lymphoma' differ in underlying genetic and clinical features from typical/atypical Burkitt's lymphoma. 'Discrepant Burkitt's lymphoma' may therefore form a distinct genetic subgroup of aggressive B-cell lymphomas, which show poor response to multi-agent chemotherapy.