Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy.
SUNY Upstate Medical University, Syracuse, NY.
JCO Precis Oncol. 2024 Aug;8:e2400200. doi: 10.1200/PO.24.00200.
Although both urachal (U) and nonurachal (NU) bladder adenocarcinomas (adenoCas) share several histologic similarities, they differ in location and sometimes in therapeutic options. We analyzed the differences in genomic alterations (GAs) between these tumor entities, with the aim of identifying potential therapeutic targets for clinical trials.
Overall, 133 U and 328 NU adenoCas were analyzed. Hybrid capture-based comprehensive genomic profiling (CGP) was performed to evaluate all classes of GA. Germline status of GA was predicted using a validated somatic-germline computational method. CGP was performed using the FoundationOne and FoundationOne CDx assays (Foundation Medicine, Inc).
The most frequent GA in both U and NU cohorts included (86.5% 81.1%) and (34.6% 27.7%). GAs characteristic of colorectal adenoCa, such as ( = .069) and ( = .071), were more common in U versus NU. Conversely, ( < .01) and ( = .071) were more prevalent in NU adenoCa. Notably, both U and NU adenoCas exhibited possibly targetable GA in (7.5% 7.9%) and (6.8% 7.6%). Biomarkers associated with potential benefit from anti-PD-1/L1 were infrequent. Median tumor mutational burden was 2.6 and 3.5 mutations per megabase for U and NU, respectively, and PD-L1 expression >1% was rare. Genomic ancestry and genomic signature distribution were similar in both tumor types. GAs were most commonly of somatic nature. Limitations include lack of clinical data, tumor heterogeneity, and retrospective nature.
U and NU adenoCAs revealed differences in GA, with and being identified as putative therapeutic targets. Biomarkers of response to anti-PD-(L)1 were uncommon. Results highlight the potential of CGP to personalize treatment options of bladder adenoCa and inform clinical trial designs.
虽然脐尿管（U）和非脐尿管（NU）膀胱腺癌（adenoCas）具有许多组织学相似之处，但它们在位置上有所不同，有时在治疗选择上也有所不同。我们分析了这两种肿瘤实体之间基因组改变（GA）的差异，旨在为临床试验确定潜在的治疗靶点。
共分析了 133 例 U 型和 328 例 NU 型腺癌。采用杂交捕获综合基因组分析（CGP）评估所有类型的 GA。使用经过验证的体细胞-种系计算方法预测 GA 的种系状态。CGP 使用 FoundationOne 和 FoundationOne CDx 检测试剂盒（Foundation Medicine，Inc.）进行。
在 U 和 NU 两组中，最常见的 GA 包括 （86.5%81.1%）和 （34.6%27.7%）。与结直肠腺癌特征相关的 GA，如 （=0.069）和 （=0.071），在 U 型中比 NU 型更为常见。相反， （<0.01）和 （=0.071）在 NU 型腺癌中更为普遍。值得注意的是，U 和 NU 型腺癌均有 （7.5%7.9%）和 （6.8%7.6%）可能具有靶向性的 GA。与抗 PD-1/L1 潜在获益相关的生物标志物并不常见。中位肿瘤突变负荷分别为 U 型和 NU 型 2.6 和 3.5 个突变/兆碱基，PD-L1 表达>1%的情况很少见。两种肿瘤类型的基因组起源和基因组特征分布相似。GA 最常见的是体细胞性质。局限性包括缺乏临床数据、肿瘤异质性和回顾性研究。
U 和 NU 型腺癌在 GA 方面存在差异，其中 和 被认为是潜在的治疗靶点。抗 PD-（L）1 反应的生物标志物并不常见。结果强调了 CGP 对膀胱腺癌个体化治疗选择的潜力，并为临床试验设计提供了信息。
