74. Genomic analyses of Hodgkin and non-Hodgkin composite lymphomas identifies shared somatic mutations indicative of common clonal origin

Aly Abdelkareem

Felicia Gomez

Dr. Gomez is an Assistant Professor in the Griffith and Fehniger Laboratories within the Department of Medicine and the Division of Oncology at Washington University School of Medicine. Dr. Gomez is leading a deep sequencing analysis of Hodgkin lymphoma genomes with the goal of describing somatic events characteristic of this malignancy. Dr. Gomez collaborates with members of the Griffith and Fehniger laboratories on projects related to the genomics of Hodgkin and Non-Hodgkin lymphomas. Dr. Gomez research goals include developing strategies to translate genomic data into improved patient care. She is specifically interested in working toward the inclusion of diverse human populations in translational genomic research


Felicia Gomeza, Lauren Sheab, Matthew Mosiorc, Kilannin Krysiaka, Yi-Shan Leea, Eric Duncavagea, Michelle O’Laughlina, Nancy Bartletta, Amanda Cashena, Malachi Griffitha, Todd Fehnigera, Lukas Wartmana, Obi Griffitha

aWashington University School of Medicine, St. Louis, MO, United States; bUniversity of Alabama at Birmingham, Birmingham, AL, United States; cMoffitt Cancer Center, Tampa, FL, United States

Composite lymphoma (CL) occurs when two lymphomas with distinct WHO subtypes arise in one patient. Here, we present two cases of CL. Case 1 presented with diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and follicular lymphoma (FL). Case 2 presented with FL and HL in two distinct areas of one lymph node. We performed exome sequencing on matched tumor/normal samples (mean depth per sample >70x) from each lymphoma, excluding the FL in case 1. SNVs and indels were filtered and manually reviewed. A subset of variants were validated using Ampliseq. In case 1, following Ampliseq, 44 DLBCL variants were confirmed and 64 HL variants were confirmed. We observed a KMT2D frameshift in DLBCL and a B2M stop gain in HL, both of which are recurrently mutated in DLBCL and HL, respectively. We report 17 shared variants including a stop gain variant in TNFRSF14. In case 2, the validated data showed 94 sites shared between the HL and FL. These shared variants include missense variants in PCLO, and a stop gain variant in TNFRSF14. We sequenced the B-cell receptor locus (BCR) in all samples. In case 1, a dominant BCR clone representing 98.7%, 74.2%, and 33.2% of rearrangements from the DLBCL, FL, and HL was detected. For case 2, a shared rearrangement was detected comprising 1.4% and 1.3% of the rearrangements in the FL and HL. In summary, the cases presented here provide evidence of a common clonal origin for two cases of Hodgkin and non-Hodgkin lymphoma CL.