Ongoing immunoglobulin somatic mutation in germinal center B cell-like butnot in activated B cell-like diffuse large cell lymphomas

B cell diffuse large cell lymphoma (B-DLCL) is a heterogeneous group of tum ors, based on significant variations in morphology. clinical presentation, and response to treatment. Gene expression profiling has revealed two disti nct tumor subtypes of B-DLCL: germinal center B cell-like DLCL and activate d B cell-like DLCL. In a separate study, we determined that B-DLCL can also be subdivided Into two groups based on the presence or absence of ongoing Ig gene hypermutation, Here, we evaluated the correlation between these B-D LCL subtypes established by the two different methods. Fourteen primary B-D LCL cases were studied by gene expression profiling using DNA microarrays a nd for the presence of ongoing mutations in their Ig heavy chain gene. All seven cases classified as germinal center B cell-like DLCL by gene expressi on showed the presence of ongoing mutations in the Ig genes. Five of the se ven cases classified by gene expression as activated B cell-like DLCL had n o ongoing somatic mutations, whereas, in the remaining two cases, a single point mutation was observed in only 2 of 15 and 21 examined molecular clone s of variable heavy (V-H) chain gene, respectively. These two cases were di stantly related to the rest of the activated B cell-like DLCL tumors by gen e expression. Our findings validate the concept that lymphoid malignancies are derived from cells at discrete stages of normal lymphocyte maturation a nd that the malignant cells retain the genetic program of those normal cell s.