Gene expression-based risk score in diffuse large B-cell lymphoma

// Caroline Bret 1,2,3 , Bernard Klein 2,3 , and Jérôme Moreaux 2 1 Department of Biological Hematology, St Eloi Hospital, Montpellier, France 2 INSERM U1040, Institute of Research in Biotherapy, Montpellier, France 3 University of Montpellier 1, UFR de Médecine, Montpellier, France Correspondence: Jérôme Moreaux, email: // Keywords : DLBCL, gene expression profile, risk score, prognosis Received : December 29, 2012, Accepted : December 30, 2012, Published : December 31, 2012 Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and displays heterogeneous clinical and molecular characteristics. In this study, high throughput gene expression profiling of DLBCL tumor samples was used to design a 12-gene expression–based risk score (GERS) predictive for patient’s overall survival. GERS allowed identifying a high-risk group comprising 46,4% of the DLBCL patients in two independent cohorts (n=414 and n=69). GERS was shown to be an independent predictor of survival when compared to the previously published prognostic factors, including the International Prognostic Index (IPI). GERS displayed a prognostic value in germinal-center B-cell–like subgroup (GCB) and activated B cell–like (ABC) molecular subgroups of patients as well as in DLBCL patients treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or Rituximab-CHOP (R-CHOP) regimens. Combination of GERS and IPI lead to a potent prognostic classification of DLBCL patients. Finally, a genomic instability gene signature was highlighted in gene expression profiles of patients belonging to the high-risk GERS-defined group.