Biomedical Frontiers: Winter 1994, Vol.1, No.2
Lymphoma Oncogene Identified

Oncogene identifications lead to improvements in cancer diagnosis, treatment, and monitoring and are key to understanding cancer pathogenesis. Thanks to research by Dr. Riccardo Dalla-Favera, Percy and Joanne Uris Professor of Pathology, et. al., BCL-6, the oncogene associated with the most prevalent type of non-Hodgkin's lymphoma (NHL), diffuse large cell lymphoma (DLCL), finally has been characterized (Science, Vol. 262, Oct. 29, 1993, p. 747).

Of immune system cancers, NHLs have the highest incidence and are the most lethal. They are the sixth leading cause of all cancer deaths in the United States. Over the past 10 years, oncogenes have been found in other NHLs. Deregulated expression of the BCL-2 and the C-MYC oncogenes plays a role in follicular and Burkitt's lymphoma, respectively. But an oncogene associated with diffuse lymphoma was not known, until now. In the Science paper, the researchers report that BCL-6 located on chromosome 3 codes for a 79 kD protein homologous with zinc finger transcription factors. Identified from a DLCL cell-line that has a chromosome 3 and 14 translocation, the scientists found other chromosomes besides 14 rearrange in DLCL and suggest the alterations cause BCL-6 overexpression. They also indicate the DLCL translocation frequency is 33 percent, although prior studies estimated 18 percent. Other lymphoid malignancies do not show BCL-6 rearrangements.

Dr. Dalla-Favera, also a professor of genetics and development, is now trying to correlate BCL-6 rearrangements with more or less aggressive DLCL. Therapeutic approaches to lymphoma could improve should he find that BCL-6 is a prognostic marker. To study normal BCL-6 function, he uses transgenic mice either overexpressing or lacking BCL-6. A patent is pending on BCL-6.

DLCL is considered the most prevalent lymphoma because follicular lymphoma often progresses to DLCL. "When physicians say someone died of lymphoma," says Dr. Dalla-Favera, "they most often mean they died of DLCL." DLCL (30 percent to 40 percent) and follicular lymphoma (30 percent to 40 percent) together account for 60 percent to 80 percent of all new lymphoma cases.

Collaborators on the study include researchers from Memorial Sloan-Kettering in New York led by Dr. R.S.K. Chaganti.