학술논문

Genomic Profiling of Prostate Cancers from Men with African and European Ancestry
Document Type
article
Source
Clinical Cancer Research. 26(17)
Subject
Genetics
Cancer
Urologic Diseases
Prostate Cancer
Aging
Human Genome
Good Health and Well Being
Adult
Black or African American
Aged
Aged
80 and over
Biomarkers
Tumor
DNA Copy Number Variations
DNA Mutational Analysis
DNA Repair
Datasets as Topic
Genomics
Health Status Disparities
Humans
Incidence
Male
Middle Aged
Mutation
Neoplasm Grading
Prostatic Neoplasms
White People
Oncology and Carcinogenesis
Oncology & Carcinogenesis
Language
Abstract
PurposeAfrican American (AFR) men have the highest mortality rate from prostate cancer (PCa) compared with men of other racial/ancestral groups. Differences in the spectrum of somatic genome alterations in tumors between AFR men and other populations have not been well-characterized due to a lack of inclusion of significant numbers in genomic studies.Experimental designTo identify genomic alterations associated with race, we compared the frequencies of somatic alterations in PCa obtained from four publicly available datasets comprising 250 AFR and 611 European American (EUR) men and a targeted sequencing dataset from a commercial platform of 436 AFR and 3018 EUR men.ResultsMutations in ZFHX3 as well as focal deletions in ETV3 were more frequent in tumors from AFR men. TP53 mutations were associated with increasing Gleason score. MYC amplifications were more frequent in tumors from AFR men with metastatic PCa, whereas deletions in PTEN and rearrangements in TMPRSS2-ERG were less frequent in tumors from AFR men. KMT2D truncations and CCND1 amplifications were more frequent in primary PCa from AFR men. Genomic features that could impact clinical decision making were not significantly different between the two groups including tumor mutation burden, MSI status, and genomic alterations in select DNA repair genes, CDK12, and in AR.ConclusionsAlthough we identified some novel differences in AFR men compared with other populations, the frequencies of genomic alterations in current therapeutic targets for PCa were similar between AFR and EUR men, suggesting that existing precision medicine approaches could be equally beneficial if applied equitably.