Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.
Foundation Medicine, Cambridge, MA.
Clin Genitourin Cancer. 2024 Feb;22(1):e163-e169.e1. doi: 10.1016/j.clgc.2023.10.008. Epub 2023 Oct 28.
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 (MYC) in advanced PCa to establish a rationale for personalized treatment combinations.
Hybrid capture-based comprehensive genomic profiling (CGP) was performed on PCa tumor samples. MYC = 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, MYC was detected in 10.6% (median CN = 8). MYC 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 MYC vs. MYC (all P < .001). In liquid samples with tumor fraction [TF]>0, MYC was detected in 2.0% (28/1,402), and 4.5% (20/445) with TF>20%. In the CGDB, (67 MYC and 658 MYC), patients received similar treatments; most received hormone therapies (35.8% MYC vs. 31.5% MYC) or chemotherapy (37.3% MYC vs. 27.7% MYC) as first therapy after CGP report.
MYC defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYC may be prognostic; independent cohorts are needed to validate these findings.
MYC 是前列腺癌（PCa）中常见的扩增潜在靶基因。我们旨在定义高级 PCa 中 MYC 扩增（MYC）的分子、免疫和临床特征，为个性化治疗组合建立依据。
对 PCa 肿瘤样本进行基于杂交捕获的综合基因组分析（CGP）。MYC=拷贝数≥6（CN）。从全国范围内匿名（280 个诊所）EHR 衍生的临床基因组数据库（CGDB）中选择了 2011 年 1 月至 2020 年 12 月间治疗的患者。
在 12528 例激素敏感和去势抵抗（CRPC）样本中，10.6%（中位数 CN=8）检测到 MYC。非洲裔男性比欧洲裔男性更常发生 MYC（12.9%比 10.2%，P=0.002），转移性组织比原发性组织更常发生 MYC（15.7%比 6.2%，P<0.001），且在转移性肝病变中富集（20.2%），但与高微卫星不稳定性呈负相关（0.8%比 2.4%，P<0.001）。MYC CN≥15 与 PD-L1 表达相关（26.1%比 9.8%，P=0.025）。与 MYC 相比，AR、RAD21、LYN、CCND1、ZNF703、FGF3/4/19 和 FGFR1 的扩增更为丰富（均 P<0.001）。在肿瘤分数[TF]>0 的液体样本中，2.0%（28/1402）和 4.5%（20/445）的 TF>20%中检测到 MYC。在 CGDB 中（67 例 MYC 和 658 例 MYC），患者接受了类似的治疗；大多数患者接受激素治疗（35.8% MYC 比 31.5% MYC）或化疗（37.3% MYC 比 27.7% MYC）作为 CGP 报告后的一线治疗。
MYC 定义了 PCa 患者的一个具有生物学特征的亚群，其特征是存在多种晚期疾病的代表。这些数据表明，MYC 可能具有预后意义；需要独立的队列来验证这些发现。
