MYC 扩增型晚期前列腺癌的分子、免疫和临床病理特征。

The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer.

机构信息

Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.

Foundation Medicine, Cambridge, MA.

出版信息

Clin Genitourin Cancer. 2024 Feb;22(1):e163-e169.e1. doi: 10.1016/j.clgc.2023.10.008. Epub 2023 Oct 28.

DOI:10.1016/j.clgc.2023.10.008

PMID:37978032

Abstract

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 (MYC) 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. 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).

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。