Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry

Autoři: Jiao Yuan aff001;  Kevin H. Kensler aff003;  Zhongyi Hu aff001;  Youyou Zhang aff001;  Tianli Zhang aff001;  Junjie Jiang aff001;  Mu Xu aff001;  Yutian Pan aff001;  Meixiao Long aff005;  Kathleen T. Montone aff006;  Janos L. Tanyi aff002;  Yi Fan aff007;  Rugang Zhang aff008;  Xiaowen Hu aff001;  Timothy R. Rebbeck aff003;  Lin Zhang aff001
Působiště autorů: Center for Research on Reproduction & Women’s Health, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff001;  Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff002;  Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America aff003;  Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts, United States of America aff004;  Department of Internal Medicine, Division of Hematology, Ohio State University, Columbus, Ohio, United States of America aff005;  Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff006;  Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff007;  Wistar Institute, Philadelphia, Pennsylvania, United States of America aff008
Vyšlo v časopise: Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry. PLoS Genet 16(2): e32767. doi:10.1371/journal.pgen.1008641
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008641


Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10−03), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10−02), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10−03). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10−48). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10−125). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1, PCAT1 and PCAT10/CTBP1-AS, were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes.

Klíčová slova:

Cancer genomics – Comparative genomics – Gene expression – Human genetics – Long non-coding RNAs – Prostate cancer – Prostate gland – Transcriptome analysis


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PLOS Genetics

2020 Číslo 2

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