Clinical applications of BAC array-CGH to the study of diffuse large B-cell lymphomas

BAC array-CGH is a powerful method to identify DNA copy number changes (gains, amplifications and deletions) on a genome-wide scale, and to map these changes to genomic sequence. It is based on the analysis of genomic DNA isolated from test and reference cell populations, the differential labelling with fluorescent dyes and the co-hybridization with a genomic array. BAC array-CGH has proven to be a specific, sensitive, and reliable technique, with considerable advantages compared to other methods used for the analysis of DNA copy number changes. The application of genome scanning technologies and the recent advances in bioinformatics tools that enable us to perform a robust and highly sensitive analysis of array-CGH data, useful not only for genome scanning of tumor cells but also in the identification of novel cancer related genes, oncogenes and suppressor genes. Cytogenetic analysis provides essential information for diagnosis and prognosis in patients with hematologic malignancies such as lymphomas. However, the chromosomal interpretation in non-Hodgkin lymphoma (NHL) is sometimes inconclusive. Copy number aberrations identified by BAC array-CGH analyses could be a complementary methodology to chromosomal analysis. In NHL the genomic imbalances might have a prognostic rather than a diagnostic value. In fact, the diagnosis of NHL is based on pathological and molecular cytogenetics data. Furthermore genetic variations and their association with specific types of lymphoma development, and elucidation of the variable genetic pathways leading to lymphoma development, are important directions for future cancer research. Array-CGH, along with FISH and PCR, will be used for routine diagnostic purposes in near future.