Title | Transcriptomes of Prostate Cancer with TMPRSS2:ERG and Other ETS Fusions. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Stopsack KH, Su XA, J Vaselkiv B, Graff RE, Ebot EM, Pettersson A, Lis RT, Fiorentino M, Loda M, Penney KL, Lotan TL, Mucci LA |
Journal | Mol Cancer Res |
Volume | 21 |
Issue | 1 |
Pagination | 14-23 |
Date Published | 2023 Jan 03 |
ISSN | 1557-3125 |
Keywords | Gene Expression Profiling, Humans, Male, Oncogene Proteins, Fusion, Prostatic Neoplasms, Proto-Oncogene Proteins c-ets, Serine Endopeptidases, Transcriptional Regulator ERG, Transcriptome |
Abstract | UNLABELLED: The most common somatic event in primary prostate cancer is a fusion between the androgen-related TMPRSS2 gene and the ERG oncogene. Tumors with these fusions, which occur early in carcinogenesis, have a distinctive etiology. A smaller subset of other tumors harbor fusions between TMPRSS2 and members of the ETS transcription factor family other than ERG. To assess the genomic similarity of tumors with non-ERG ETS fusions and those with fusions involving ERG, this study derived a transcriptomic signature of non-ERG ETS fusions and assessed this signature and ERG-related gene expression in 1,050 men with primary prostate cancer from three independent population-based and hospital-based studies. Although non-ERG ETS fusions involving ETV1, ETV4, ETV5, or FLI1 were individually rare, they jointly accounted for one in seven prostate tumors. Genes differentially regulated between non-ERG ETS tumors and tumors without ETS fusions showed similar differential expression when ERG tumors and tumors without ETS fusions were compared (differences explained: R2 = 69-77%), including ETS-related androgen receptor (AR) target genes. Differences appeared to result from similarities among ETS tumors rather than similarities among non-ETS tumors. Gene sets associated with ERG fusions were consistent with gene sets associated with non-ERG ETS fusions, including fatty acid and amino acid metabolism, an observation that was robust across cohorts. IMPLICATIONS: Considering ETS fusions jointly may be useful for etiologic studies on prostate cancer, given that the transcriptome is profoundly impacted by ERG and non-ERG ETS fusions in a largely similar fashion, most notably genes regulating metabolic pathways. |
DOI | 10.1158/1541-7786.MCR-22-0446 |
Alternate Journal | Mol Cancer Res |
PubMed ID | 36125519 |
PubMed Central ID | PMC9812892 |
Grant List | P50 CA090381 / CA / NCI NIH HHS / United States U01 CA167552 / CA / NCI NIH HHS / United States R01 CA136578 / CA / NCI NIH HHS / United States R01 CA141298 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.