膀胱小细胞癌与尿路上皮癌和小细胞肺癌的比较基因组特征。

IF 5.6 2区 医学 Q1 ONCOLOGY
JCO precision oncology Pub Date : 2025-04-01 Epub Date: 2025-04-10 DOI:10.1200/PO-24-00947
Salvador Jaime-Casas, Neal S Chawla, Nicholas J Salgia, Benjamin Mercier, Ameish Govindarajan, Xiaochen Li, Daniela V Castro, Hedyeh Ebrahimi, Regina Barragan-Carrillo, Peter D Zang, Alexis LeVee, Miguel Zugman, Nazli Dizman, JoAnn Hsu, Luis Meza, Zeynep Zengin, Alexander Chehrazi-Raffle, Tanya Dorff, Sumanta K Pal, Abhishek Tripathi
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引用次数: 0

摘要

目的:小细胞膀胱癌(SCBC)是一种罕见的膀胱癌的组织学变异,病程具有侵袭性,预后较差。鉴于其不常见的性质,目前缺乏表征该疾病基因组驱动因素的高质量数据,并且大多数患者的治疗方法反映了小细胞肺癌(SCLC)。利用Tempus Lens确定的临床注释基因组数据集,我们试图评估SCBC相对于尿路上皮癌(UC)和SCLC的突变景观。方法:通过Tempus试验对任何阶段的SCBC、UC和SCLC患者进行血液或组织基因组分析,并对这些患者的躯体致病性基因组改变进行编目。比较不同组织学组的基线临床和人口学特征。使用描述性统计对变更进行整理和汇总。进行两两比较以评估病理队列中突变频率的差异。结果:研究共纳入149例SCBC、4350例UC和1697例SCLC患者。SCBC中最常见的基因组改变是TP53(87%)、TERT(75%)和RB1(70%)。在TP53突变的SCBC患者中,77%的患者出现RB1突变。与UC相比,SCBC患者的TP53、RB1、KMT2D和KDM6A突变显著富集。与SCLC相比,SCBC患者在TERT、ARID1A和CREBBP等突变中富集(P < 0.05)。在SCBC中观察到多种临床可靶向突变,包括PIK3CA(19%)、ERBB2/3(13%)和ALK(10%)。本研究的局限性包括其回顾性。结论:该研究代表了迄今为止对SCBC特征进行的最广泛的研究之一,提供了对该疾病潜在的基因组改变的新理解,并揭示了可作为改善临床结果的潜在靶点的可操作突变。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative Genomic Characterization of Small Cell Carcinoma of the Bladder Compared With Urothelial Carcinoma and Small Cell Lung Carcinoma.

Purpose: Small cell bladder cancer (SCBC) is a rare histologic variant of bladder cancer with an aggressive disease course and poor outcomes. Given its uncommon nature, there is a paucity of high-quality data characterizing genomic drivers of this disease, and most patients are treated with approaches mirroring small cell lung cancer (SCLC). Leveraging the Tempus Lens deidentified clinically annotated genomic data set, we sought to evaluate the mutational landscape of SCBC relative to urothelial carcinoma (UC) and SCLC.

Methods: Somatic pathogenic genomic alterations in patients with SCBC, UC, and SCLC of any stage who underwent blood- or tissue-based genomic profiling through the Tempus assay were cataloged. Baseline clinical and demographic features were compared across histologic groups. Alterations were collated and summarized using descriptive statistics. Pairwise comparisons were performed to assess differences in mutation frequency across pathologic cohorts.

Results: In total, 149 SCBC, 4,350 UC, and 1,697 SCLC patients were included in the study. The most common genomic alterations in SCBC were in TP53 (87%), TERT (75%), and RB1 (70%). Among SCBC patients with TP53 mutations, RB1 comutations were observed in 77% of patients. Compared with UC, SCBC patients were significantly enriched for TP53, RB1, KMT2D, and KDM6A mutations. Compared with SCLC, SCBC patients were enriched for TERT, ARID1A, and CREBBP mutations, among others (P < .05). Multiple clinically targetable mutations were observed in SCBC, including PIK3CA (19%), ERBB2/3 (13%), and ALK (10%). Limitations of this study include its retrospective nature.

Conclusion: This study represents one of the most extensive efforts to characterize SCBC to date, providing a novel understanding of the genomic alterations underlying the disease and revealing actionable mutations that could serve as potential targets for improved clinical outcomes.

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CiteScore
9.10
自引率
4.30%
发文量
363
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