Abstract 829P
Background
Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin lymphoma that is defined by unique somatic mutation and gene expression profile. Differences in the genomic profile of FL by age and by sex have not been well characterized.
Methods
We analyzed data from 155 patients with FL who underwent next generation sequencing and RNA expression analysis using the Genomic Testing Cooperative Hematology Plus platform. The DNA and RNA panels assessed 179 genes and 1408 genes, respectively. Our analysis was based on sex (male n=75, female n=80) and age (<50 years, n=20; 50-74 years, n=109; >75 years, n=26). Data and statistics were analyzed with Bioconductor R package Maftools and Broad Institute Gene Set Enrichment Analysis.
Results
At least one somatic mutation in epigenetic genes: KMT2D (n=106), CREBBP (n=98), EZH2 (n=41) and EP300 (n=27) were present in 95% of all patients (n=155). Mutations in B2M were significantly enriched in females (10% vs 1.3%, p=0.035), while mutations in MEF2B were significantly enriched in males (24% vs 10%, p=0.030). Mutations in EP300 were enriched in the young cohort (<50; 35% vs 14%, p=0.047). Mutations in genes: BCR (Breakpoint Chain Region; 23% vs 3.9%, p=0.0033), CREBBP (81% vs 60%, p=0.047), STAT6 (23% vs 8.5%, p=0.042) and TET2 (19% vs 6.2%, p=0.045) were enriched in the elderly cohort (>75). All BCR mutations (missense and truncations), occurred within the N-terminus kinase domain of the gene. These mutations have not been well characterized in FL and are predicted to be deleterious; involving a coiled-coil domain essential for oligomerization and gene function. These mutations may compromise its function as a regulator of RAC1 and RHOA proteins. Correlation with limited available clinical data also suggests that these mutations are seen with aggressive FL or FL undergoing transformation. RNA expression did not show any significant differences based on age or sex.
Conclusions
Our study suggests that there are age and gender specific genomic alterations in FL. We plan to follow up with validation studies in a larger cohort.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Genomic Testing Cooperative.
Funding
Has not received any funding.
Disclosure
A. Novak: Other, Personal, Funding, Research funding: Bristol Myers Squibb. M. Albitar: Financial Interests, Personal, Leadership Role, CEO, CMO and own stocks: Genomic Testing cooperative. H. Tun: Financial Interests, Personal and Institutional, Research Grant: Gossamar Bio, Acrotech; Financial Interests, Personal, Advisory Board: Curis. All other authors have declared no conflicts of interest.
Resources from the same session
947P - The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma: A phase Ib/II clinical trial
Presenter: Li Bai
Session: Poster session 18
949P - Regorafenib combined with immunotherapy versus regorafenib as second-line therapy in patients with advanced hepatocellular carcinoma: A multicenter real-world study
Presenter: Bin-Kui Li
Session: Poster session 18
952P - Efficacy and safety of a PRospective, Observational trial of Lenvatinib cOmbined with transarterial chemoembolization (TACE) as initial treatment for advaNced staGe hepatocellular carcinoma (PROLONG): A multicenter, single-armed, real-world study
Presenter: Guoliang Shao
Session: Poster session 18
953P - Tislelizumab plus regorafenib as second-line therapy for unresectable hepatocellular carcinoma (uHCC): A single-arm, phase II trial
Presenter: Zhongchao Li
Session: Poster session 18
954P - Radiotherapy combined with tislelizumab plus anlotinib as first-line treatment for hepatocellular carcinoma: A single arm, phase II clinical trial
Presenter: Guishu wu
Session: Poster session 18
955P - IMMUNIB trial (AIO-HEP-0218/ass): A single-arm phase II study evaluating safety and efficacy of immunotherapy with nivolumab in combination with lenvatinib in advanced hepatocellular carcinoma
Presenter: Arndt Vogel
Session: Poster session 18
956P - Phase II study of adjuvant tislelizumab combined with interferon-α and active surveillance in hepatocellular carcinoma patients with microvascular invasion
Presenter: Yixiu Wang
Session: Poster session 18