Journal article
The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer
Clinical genitourinary cancer, Vol.22(1), pp.e163-e169.e1
02/2024
DOI: 10.1016/j.clgc.2023.10.008
PMID: 37978032
Abstract
MYC is a commonly amplified, potentially targetable gene in prostate cancer (PCa). We sought to define the molecular, immunologic, and clinicodemographic landscape of MYC amplification (MYCamp) in advanced PCa to establish a rationale for personalized treatment combinations.
Hybrid capture-based comprehensive genomic profiling (CGP) was performed on PCa tumor samples. MYCamp = copy number ≥6 (CN). Patients treated between January 2011 and December 2020 were selected from a nationwide deidentified (280 clinics) EHR-derived clinicogenomic database (CGDB).
Of 12,528 hormone-sensitive and castrate-resistant (CRPC) samples, MYCamp was detected in 10.6% (median CN = 8). MYCamp was more frequent in men with African versus European ancestry (12.9% vs. 10.2% P = .002), in metastatic vs. primary tissue (15.7% vs. 6.2% P < .001), and enriched in metastatic liver lesions (20.2%), but inversely associated with high microsatellite-instability (0.8% vs. 2.4%, P < .001). MYC CN≥15 was associated with PD-L1 expression (26.1% vs. 9.8%, P = .025). Amplification of AR, RAD21, LYN, CCND1, ZNF703, FGF3/4/19, and FGFR1 was enriched in MYCamp vs. MYCwt (all P < .001). In liquid samples with tumor fraction [TF]>0, MYCamp was detected in 2.0% (28/1,402), and 4.5% (20/445) with TF>20%. In the CGDB, (67 MYCamp and 658 MYCwt), patients received similar treatments; most received hormone therapies (35.8% MYCamp vs. 31.5% MYCwt) or chemotherapy (37.3% MYCamp vs. 27.7% MYCwt) as first therapy after CGP report.
MYCamp defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYCamp may be prognostic; independent cohorts are needed to validate these findings.
We profiled the genomes of over 12,000 advanced prostate cancer samples and probed a large clinicogenomic database with ∼1000 patients to clarify the impact MYCamp in PCa. Results suggest that MYCamp advanced PCa has limited targeted therapies and is an aggressive subset of advanced prostate cancer found disproportionately more common in men with African ancestry.
Details
- Title: Subtitle
- The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer
- Creators
- Will H. Jin - University of MiamiLiangliang Zhang - Foundation MedicineRyon Graf - Foundation MedicineKira Raskina - Foundation MedicineHanna Tukachinsky - Foundation MedicineRichard S.P. Huang - Foundation MedicineKimberly McGregor - Foundation MedicineMohamed Alshalalfa - University of MiamiHelen Y. Hougen - Sylvester Comprehensive Cancer CenterAnwar Khan - Sylvester Comprehensive Cancer CenterSanoj Punnen - Sylvester Comprehensive Cancer CenterAlexa B. Schrock - Foundation MedicineJeffrey Venstrom - Foundation MedicineBrandon A. Mahal - Sylvester Comprehensive Cancer Center
- Resource Type
- Journal article
- Publication Details
- Clinical genitourinary cancer, Vol.22(1), pp.e163-e169.e1
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.clgc.2023.10.008
- PMID
- 37978032
- ISSN
- 1558-7673
- eISSN
- 1938-0682
- Language
- English
- Date published
- 02/2024
- Academic Unit
- Urology
- Record Identifier
- 9984701556402771
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