Abstract 4206: Examining genetic ancestry in diffuse large B-cell lymphoma (DLBCL)
Authors: Lee Michelle J. , Jhaney Camber Ileen , Flowers Christopher R. , Koff Jean L. 
Published: August 2019

Background: There are significant racial differences in incidence and outcomes for DLBCL in the United States, and African American patients (pts) present at a younger median age (54 vs. 65 years), more commonly at advanced stage, and have inferior 5-year survival compared to white pts (Shenoy et al., 2011). It is unclear if there are inherent genomic differences contributing to the survival disparities in African American pts compared with white pts.

Methods: Using whole exome sequencing data of 1,001 DLBCL pts (Reddy et al., 2013), we performed quality control of samples (heterozygosity, missingness &gt;10%) and single nucleotide variants (SNVs; missingness &gt;20%) with PLINK. For global ancestry estimation, we used unsupervised model-based ADMIXTURE with K=3 postulated ancestral populations and examined correlations with 21 pts (17 African-American, 2 White, and 2 Hispanic) with self-reported race. Pt characteristics (age, gender, serum lactate dehydrogenase, tumor stage, ECOG performance status, number of extranodal sites of disease, B symptoms, International Prognostic Index score, RNA-sequencing based molecular subtype) and survival were compared across ancestry groups. We examined ancestry differences in mutational patterns and frequency of top 20 driver genes. Chi-squared tests and ANOVA were used for the analysis of pt characteristics and clinical pathological features across ancestry groups. Multivariate Cox regression analyses were used to evaluate prognostic factors.

Results: ADMIXTURE global ancestry prediction had 100% correlation with self-reported race and identified 619 pts with &gt;90% European ancestry, 81 with &gt;90% African ancestry, and 43 with &gt;90% Asian ancestry. DLBCL pts with &gt;90% African ancestry had an age at diagnosis 10 years younger (p &lt; 0.001), more commonly had B symptoms (p &lt; 0.001), more commonly had elevated LDH (p &lt; 0.001), more commonly had extranodal sites of involvement (p = 0.001), and more commonly had advanced stage diseases (p = 0.007) compared to patients with &gt;90% European ancestry. There were no statistical differences between these ancestry groups in gender, ECOG, IPI score, and molecular subgroup (ABC/GCB/Unclassified). The total variant distribution (missense, truncation, CNV gain, CNV loss) was similar between patients with &gt;90% European ancestry and &gt;90% African ancestry, and only HIST1H1E copy number loss and MGA missense mutations were significantly more common in patients with African ancestry.

Conclusions: Additional studies examining the differentially mutated genes or other factors in African American DLBCL pts may explain comparatively adverse features and outcomes for African American pts.

Citation Format: Michelle J. Lee, Camber Ileen Jhaney, Christopher R. Flowers, Jean L. Koff. Examining genetic ancestry in diffuse large B-cell lymphoma (DLBCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4206.