Abstract
Simple SummaryGenomic prognostic biomarkers play an important role in the application of precision medicine in patients with uveal melanoma (UM). In this study, we performed a pilot study to assess the impact of global and local genetic ancestry on the presence of these prognostic biomarkers. We found a trend for correlations between high risk biomarkers and European ancestry. These results highlight the need for a rigorous genetic ancestry methodology to study the role of ancestry in determining prognosis in patients with UM.Uveal melanoma (UM) is the most common cancer of the eye and leads to metastatic death in up to half of patients. Genomic prognostic biomarkers play an important role in clinical management in UM. However, research has been conducted almost exclusively in patients of European descent, such that the association between genetic admixture and prognostic biomarkers is unknown. In this study, we compiled 1381 control genomes from West African, European, East Asian, and Native American individuals, assembled a bioinformatic pipeline for assessing global and local ancestry, and performed an initial pilot study of 141 UM patients from our international referral center that manages many admixed individuals. Global and local estimates were associated with genomic prognostic determinants. Expression quantitative trait loci (eQTL) analysis was performed on variants found in segments. Globally, after correction for multiple testing, no prognostic variable was significantly enriched in a given ancestral group. However, there was a trend suggesting an increased proportion of European ancestry associated with expression of the PRAME oncogene (q = 0.06). Locally enriched European haplotypes were associated with the poor prognosis class 2 gene expression profile and with genes involved in immune regulation (q = 4.7 × 10−11). These findings reveal potential influences of genetic ancestry on prognostic variables, implicate immune genes in prognostic differences based on ancestry, and provide a basis for future studies of admixed patients with UM using rigorous genetic ancestry methodology.
Highlights
Precision medicine is transforming oncology through the use of genomic biomarkers to guide diagnosis, risk stratification, and therapeutic choices [1,2]
It has been shown that cancers differ according to prognostically relevant genomic aberrations based on genetic ancestry [5] which could affect the accuracy of genomic testing and effectiveness of targeted therapy
This study aims to explore a potential correlation between genetic ancestry and prognostic determinants in Uveal melanoma (UM)
Summary
Precision medicine is transforming oncology through the use of genomic biomarkers to guide diagnosis, risk stratification, and therapeutic choices [1,2]. It has been shown that cancers differ according to prognostically relevant genomic aberrations based on genetic ancestry [5] which could affect the accuracy of genomic testing and effectiveness of targeted therapy. This finding is especially critical in countries like the United. Uveal melanoma (UM) is an aggressive cancer of the eye in which precision genomic biomarkers have become the standard of care for risk stratification and patient management [7]. The UM genomic landscape can be divided into two major prognostic groups based on gene expression profile (GEP)
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