التفاصيل البيبلوغرافية
| العنوان: |
The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer. |
| المؤلفون: |
Jin, Will H., Liangliang Zhang, Graf, Ryon, Raskina, Kira, Tukachinsky, Hanna, Huang, Richard S. P., McGregor, Kimberly, Alshalalfa, Mohamed, Hougen, Helen Y., Khan, Anwar, Punnen, Sanoj, Schrock, Alexa B., Venstrom, Jeffrey, Mahal, Brandon A. |
| المصدر: |
Clinical Genitourinary Cancer; Feb2024, Vol. 22 Issue 1, pe163-e169.e1, 8p |
| مصطلحات موضوعية: |
PROSTATE cancer treatment, PROSTATE cancer & genetics, GENE amplification, CASTRATION-resistant prostate cancer, PROGRAMMED death-ligand 1 |
| مستخلص: |
We profiled the genomes of over 12,0 0 0 advanced prostate cancer samples and probed a large clinicogenomic database with ~10 0 0 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. Background: 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. Methods: 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). Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Clinical Genitourinary Cancer is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
