Nucleotide excision DNA repair pathway as a therapeutic target in patients with high-risk diffuse large B cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. DLBCL is a molecularly heterogeneous disease, and the addition of Rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) has significantly improved the survival of patients. Gene expression profiling studies revealed that DLBCL comprises two main subgroups displaying distinct molecular gene signatures and clinical outcome: one subgroup, termed germinal-center B-cell-like (GCB), associated with a gene expression profile (GEP) of healthy germinal-center B cells and with a good outcome, and another subgroup, termed activated B-cell-like (ABC), with GEP of healthy peripheral blood activated B cells and with a poorer outcome. GCB and ABC subgroups represent 50% and 30%, respectively, of DLBCL cases. The residual 20% of patients are unclassifiable. We used previously described methods to build powerful risk scores in hematological malignancies and designed a 12-gene expression-based risk score (GERS) predictive for overall survival (OS) in two independent cohorts of patients with DLBCL. GERS allows identifying 12.3% of patients within GCB and high risk and 33.7% of patients within ABC and high risk. GERS is an independent prognostic factor when compared with previously published factors, including the International Prognostic Index (IPI). Of interest, GERS allows identifying high-risk patients with a median OS of 24.6 and 14.3 mo when treated Nucleotide excision DNA repair pathway as a therapeutic target in patients with high-risk diffuse large B cell lymphoma