Comparative analysis of prognostic molecular signatures in Asian and Caucasian AML populations.

Abstract

e13025 Background: Next generation sequencing (NGS) studies on various cancer types have revealed clinical insights on the molecular etiology of tumors and defined new treatment paradigms. However, the genomic landscape of a tumor type may be predicated on race. Application of broad-brush findings from one population to another may lead to erroneous treatment decisions. While the majority of published NGS cancer studies focus on Caucasian populations, few studies evaluate the molecular profiles of a tumor type between different demographies. In this study, acute myeloid leukemia (AML) patients of East Asian descent were sequenced at a South Korean hospital, interpreted, and compared with the Caucasian population from The Cancer Genome Atlas (TCGA). Methods: 23 South Korean AML patients were sequenced in 2018 using the 54 gene Illumina TruSight Myeloid Panel at Hallym University, College of Medicine. Orthogonal testing for FLT3-internal tandem duplication (ITD) was done by Sanger sequencing. Watsonä for Genomics (WfG), an artificial intelligence decision-support system, was used for variant interpretation and annotation. Additionally, 181 AML patients of Caucasian descent from the TCGA dataset were analyzed for comparison. Results: WfG identified at least 1 clinically actionable therapeutic alteration in 70% (16/23) of all Asian cohort cases. FLT3-ITD or tyrosine kinase domain (TKD) mutations were reported in 27% (49/181) of cases in the TCGA cohort but only 9% (2/23) of the Asian cohort. DNMT3A mutations were detected in 25% (45/181) and 74% (17/23) of the TCGA and Asian cohorts, respectively. Other oncogenic mutations in AML including NRAS, IDH1, IDH2, CEBPA, TET2, and NPM1 were represented at comparable frequencies between the two populations. Conclusions: Tumor biomarkers that affect prognosis can be informative in the clinical setting. In our study, FLT3 and DNMT3A, predictors of poor prognosis in AML, demonstrated decreased and increased respective frequencies in South Koreans compared to Caucasians, suggesting that some mutational signatures that predict cancer outcome may vary by race.