Scientists identify six genes associated with the most common form of non-Hodgkin's lymphoma

In a paper that will be published on Thursday, April 29, 2004 in the New England Journal of Medicine, a team of scientists from Stanford University and Applied Biosystems, an Applera Corporation business, describe the identification of six genes associated with survival in diffuse large B cell lymphoma (DLBCL), the most common form of non-Hodgkin's lymphoma.

The paper, entitled "Prediction of survival in diffuse large B-cell lymphoma based on the expression of six genes," presents an analysis of 36 genes that had been associated in other studies with survival in DLBCL and which were selected from among more than 10,000 candidate genes. This study is the first to identify a set of specific genes whose activity correlates with survival, and which were previously associated with this disease in multiple published studies employing a variety of molecular, biological, or technical methods.

Expression profiles for these 36 genes were measured in 66 independent DLBCL tumor samples using real-time PCR and the Applied Biosystems TaqMan® Gene Expression Assays on an ABI PRISM® 7900HT Sequence Detection System. Together, this system enables rapid, accurate, and cost-effective discovery and validation of gene expression patterns in complex diseases. The genes most predictive of overall survival in DLBCL were LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2.

"These findings are interesting because they propose that molecular profiling may help refine prognoses in this difficult-to-treat blood cancer," said Ronald Levy, MD, Professor of Medicine and lead author, Stanford University Medical Center. "Currently, physicians rely on the International Prognostic Index (IPI) to evaluate patients with DLBCL. This predictive index is based on clinical factors including age, stage of the tumor, and the presence of disease that has spread outside the point of origin. While the IPI provides a standard way to evaluate cases of DLBCL, clinical outcomes among DLBCL patients with identical IPI values vary considerably. We look forward to further exploration of this model by replicating the study in a larger and more diverse population. The ultimate goal is that these profiles may lead to insights that could eventually be applicable toward the development of new medicines, as well as to improved means of matching patients with appropriate treatment regimens."

Diffuse large B-cell lymphoma is the most common type of lymphoma in adults, with an annual incidence in the United States of more than 25,000 cases, accounting for 30-40% of cases of non-Hodgkin's lymphomas. While combination chemotherapy has improved treatment outcomes, currently fewer than half of DLBCL patients achieve durable remission.

"These findings provide an important example of the practical applications for the latest genomic technologies and the type of research that is at the interface of basic and clinical research," said Michael W. Hunkapiller, Ph.D., President of Applied Biosystems. "Applied Biosystems is pleased to have worked with Dr. Levy and his colleagues in planning and executing these studies, and we look forward to collaborating with other clinical researchers to further advance the field of disease research."