Genomic Profiling and Clinicopathological Features in Peruvian Patients with EBV-Positive Diffuse Large B-Cell Lymphomas, NOS

Abstract

Introduction: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is a newly recognized entity by the World Health Organization. EBV+ DLBCL, NOS is commonly encountered in Latin American countries and carries a dismal prognosis. It has been published studies that have evaluated the genetic profiling in EBV +DLBCL from Asian and Western countries. However, there are lacking of studies from Latin America. This study aimed to characterize and compare the genetic profiling and clinicopathological features in Peruvian EBV+ with EBV- DLBCL patients. Methods: This retrospective cohort study included patients ≥18 years from one institution in Peru from 2010 to 2020. Hematopathologists reviewed pathological samples to confirm the diagnosis of EBV+ DLBCL cases. An EBV+ case was confirmed when the EBER test had a positivity more or equal to 40%. We collected clinicopathological data by reviewing the medical records of the patients. Twenty paraffin-embedded biopsy samples were analyzed and tumor DNA was purified using silica columns (QIAGEN, Valencia, CA, USA). The quantity and quality of the purified DNA were evaluated by spectrophotometry. We compared the genetic profiling with ten EBV+ versus ten EBV- DLBCL samples. Results: Twenty-two candidate genes were selected from previous reports of exome analysis with the diagnosis of DLBC. The median age at diagnosis was similar in both groups (58 years old, range 19-89). There was a male predominance in EBV+ (57%) compared to EBV- DLBCL cases (43%). Sixty-eight percent of patients with EBV+ had advanced disease (Ann arbor stage III-IV), compared to 48% of EBV- DLBCL patients. The non-germinal center was more common in EBV+ (60%) than EBV- cases (40%). All patients received either R-CHOP-like regimens as a first-line treatment. The overall response rate was 91% for EBV- compared to 74% for EBV+ DLBCL. We found mutations in MYC (10%), NOTCH2 (5%), STAT6 (5%) , ANKRD11(5%), TP53 (5%), KMT2A (5%), YY1 (5%), CARD11 (5%), ARID1A (5%) and RHOA (5%) in EBV+ cases, meanwhile, ARID1A (10%) , CCR6 (10%), KMT2A (5%), CARD11(5%), NOTCH2 (5%), TP53 (5%), and ANKRD11(5%) in EBV - DLBCL cases. Conclusions: This is the first Latin American study that have performed the genomic pattern in Peruvian EBV+ in comparison to EBV- DLBCL patients. Overall, our data suggest that Peruvian EBV+ DLBCL have different genetic profiling compared to East and Western countries. Also, we found that EBV+ and EBV- patients share similar drive mutations. Our findings should be validated in a larger prospective cohort of Latin American patients.