829P - Age and sex related genomic profiles of follicular lymphoma

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.