Abstract
Purpose :
Uveal melanoma (UM) is the most common eye cancer in adults. UM is a deadly cancer in which recent genetic discoveries have led to a revolution in precision prognostic testing and targeted therapy. These advances however have only been validated in white patients of northern European ancestry. Hispanics represent the fastest growing racial/ethnic minority group in the US. Hispanics are the second largest most common group of people afflicted by uveal melanoma. It remains unclear how genetic ancestry may impact current prognostic biomarkers and patient outcomes.
Methods :
The peripheral blood from a cohort of 96 patients with UM was obtained and processed. This cohort was comprised of 40 self-reported white non-Hispanic, 51 Hispanic, and 5 non-white non-Hispanic UM patients. Leukocyte DNA from each patient was genotyped, generating whole genome single nucleotide polymorphism (SNP) profiles. Quality control was performed keeping only bi allelic SNPs and SNP call rate of >98%. Global ancestral estimates, using greater than 400,000 SNPs, were calculated against reference samples from West African, East Asian, European, and Native American ancestral populations. He genomic diversity space was generated via principal component analysis of all 96 UM patient samples. ADMIXTURE was used to estimate the ancestral proportions among the UM patients. SNPs were phased and local ancestral calls were calculated on each patient.
Results :
The genetic structure of individual patient samples revealed a diverse ancestral admixture among self-reported Hispanic patients with UM. We found that patients with <90% European ancestry had a lower risk of metastasis and better clinical outcome than those with >90% European ancestry. Preliminary analysis of admixture mapping revealed areas of African and Native American ancestry with nominal significance that are associated with better prognostic biomarkers.
Conclusions :
These findings present an exciting opportunity for studying ancestral genetic determinants on patient outcome in UM. The results show that genetic ancestry may influence the occurrence and clinical significance of prognostic biomarkers and patient outcomes in UM. Utilizing genetic ancestry may aid in our understanding and guide future management of ocular pathologies in admixed individuals.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.