c-myc mRNA expression and genomic alterations in mantle cell lymphomas andother nodal non-Hodgkin's lymphomas

Cyclin D1 is a weak oncogene that cooperates with c-myc activation in the d evelopment of B cell lymphomas in transgenic animals. Cyclin D1 is constant ly overexpressed in human mantle cell lymphomas (MCL). However, the status of c-myc gene in these tumors is not known. We have examined the c-myc mRNA expression and genomic alterations, including mutational analysis of exon 1, intron 1, and exon 2 regulatory elements, in a series of 33 MCL, 22 typi cal and 11 blastoid variants. In addition, c-myc alterations were also exam ined in 56 nodal non-Hodgkin's lymphomas (NHL), c-myc mRNA overexpression w as found in 38% (11/29) of MCL with a slightly higher frequency in blastoid Variants (5/10, 50%) than in typical cases (6/19, 31%). Genetic alteration s were only found in one blastoid MCL showing a three-fold c-myc gene ampli fication. In other nodal NHL, c-myc overexpression was found in 24% (7/29) of indolent tumors but in 70% (19/27) of aggressive variants. c-myc Genetic alterations detected in these cases were gene rearrangement and hypermutat ions in one Burkitt's lymphoma, and individual point mutations in intron 1 or exon 2 in 1/19 (5%) indolent and 7/16 (44%) aggressive variants. These r esults indicate that c-myc is overexpressed in a subset of MCL, but structu ral gene alterations are less frequent than in other nodal NHL.