Genome-wide knowledge of gene expression in cancer cells promises to illuminate many aspects of their clinical behaviour. We have begun a study of gene expression in lymphoid malignancies by constructing a specialized cDNA microarray, termed the ‘Lymphochip’, that is enriched in genes selectively expressed in lymphocytes and genes regulating lymphocyte function. As most human lymphomas appear to represent malignant transformation of the germinal center B lymphocyte, we created a cDNA library from germinal center B lymphocytes purified by flow sorting from human tonsils. We obtained 50,000 sequences from this library, over 10% of which had not been observed previously in other libraries. This rich source of novel genes formed the basis of the Lymphochip microarray, which currently contains over 15,000 clones.
Initial experiments with the Lymphochip have focused on two B cell malignancies: diffuse large cell lymphoma, a common and aggressive subtype of non-Hodgkin lymphoma, and chronic lymphocytic leukaemia. We chose these malignancies for study because they most likely encompass a variety of molecularly distinct diseases that cannot be distinguished morphologically. Disease-specific sets of genes were identified that were characteristically expressed in all cases of one malignancy and not the other. Nonetheless, substantial variation in gene expression was observed between cases in a given diagnostic group, which could be used to define novel diagnostic subgroups.
This is a preview of subscription content, access via your institution