TY - JOUR
T1 - Impact of genetic ancestry on prognostic biomarkers in uveal melanoma
AU - Rodriguez, Daniel A.
AU - Sanchez, Margaret I.
AU - Decatur, Christina L.
AU - Correa, Zelia M.
AU - Martin, Eden R.
AU - Harbour, J. William
N1 - Funding Information:
Funding: This work was supported by National Cancer Institute grants R01CA125970 (J.W.H.), F31CA243426 (D.A.R.) and P30CA240139 (Sylvester Comprehensive Cancer Center), NIH Core Grant P30EY014801 (Bascom Palmer Eye Institute), Research to Prevent Blindness Unrestricted Grant (Bascom Palmer Eye Institute), and a generous gift from Mark J. Daily (J.W.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding organizations had no role in the design or conduct of this research.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Admixture
KW - Ancestry
KW - Biomarkers
KW - Genetics
KW - Uveal melanoma
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U2 - 10.3390/cancers12113208
DO - 10.3390/cancers12113208
M3 - Article
C2 - 33142712
AN - SCOPUS:85094850046
SN - 2072-6694
VL - 12
SP - 1
EP - 13
JO - Cancers
JF - Cancers
IS - 11
M1 - 3208
ER -