Abstract
BackgroundDespite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL.MethodsWe analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients.ResultsWe identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis.ConclusionCOMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL.Trial RegistrationClinicalTrials.gov NCT01502982
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm
Patients The prospectively collected screening and tissue microarray (TMA) cohorts consisted of diffuse large B-cell lymphoma (DLBCL) patients who were less than 65 years old and had primary high-risk (ageadjusted International Prognostic Index score 2–3) disease
They were treated in the Nordic phase II NLG-LBC-04 protocol with six courses of R-CHOEP14 followed by systemic CNS prophylaxis with one course of high-dose methotrexate and one course of high-dose cytarabine [18]
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm. It is an aggressive lymphoma entity, and only 50% of patients can be cured with anthracycline-based CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like chemotherapy. Following the addition of rituximab or etoposide to CHOP, or the administration of CHOP dose-densely at two-week intervals (CHOP-14), response rates and survival have significantly improved [1,2,3,4,5]. Despite these advances, 20–30% of patients experience disease relapses or have primary refractory disease. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL
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