By Peter Martin, MD and Olivier Elemento, PhD
Based on multiple randomized phase 3 studies initiated over a decade ago, R-CHOP chemotherapy is the standard of care for first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL). However, sometimes R-CHOP is not successful. Fortunately, our understanding of lymphoma has evolved over the past decade.
It is increasingly clear that “DLBCL” is a heterogeneous group of related tumors. Studies using gene expression profiling , have revealed that DLBCL can be divided into three subgroups based on the probable cell of origin (i.e., the cell from which the lymphoma was derived): activated B-cell like DLBCL (ABC), germinal center-like DLBCL (GCB), and a third group, termed “type 3”, that doesn’t possess any specific characteristics (click here to read the abstract). So far, the clinical relevance of differentiating between the ABC and GCB subtypes of DLBCL remains somewhat unclear. Nonetheless, studies done at Weill Cornell Medical College and elsewhere have suggested that certain treatments might preferentially benefit one subtype (see here and here). As a result, ongoing clinical trials are evaluating newer therapies targeted to the appropriate subgroup.
Just as we are beginning to understand the significance of DLBCL gene expression profiles, recent technological advances in DNA sequencing are making the rapid, high-resolution sequencing of a tumor’s entire genome (DNA code) possible and affordable . Two recently published papers describe the results of long-term efforts by two different groups to sequence the genome of DLBCL tumors.
A Groundbreaking Study
In a paper entitled “Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma” published in the journal Nature, Gascoyne, Marra and colleagues describe the results of a groundbreaking study. The researchers sequenced the entire DNA code from lymphoma tumors and compared the results to normal DNA obtained from the same patients. They were able to identify several genes that were mutated in the tumors but not in the normal DNA. Using these data, they were able to identify 109 genes with a potential role in lymphoma. Continue reading “Lymphoma in the News: Two Important Studies Take Us One Step Closer to Personalized Lymphoma Therapy”