具有小细胞组织学特征的尿路上皮癌具有明确的高肿瘤突变负担、频繁的 TP53 和 RB 突变以及独特的基因表达谱。
Urothelial Cancers with Small Cell Variant Histology Have Confirmed High Tumor Mutational Burden, Frequent TP53 and RB Mutations, and a Unique Gene Expression Profile.
机构信息
Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA; Department of Urology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
The James Buchanan Brady Urological Institute, Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
出版信息
Eur Urol Oncol. 2021 Apr;4(2):297-300. doi: 10.1016/j.euo.2019.12.002. Epub 2020 Feb 13.
Although predominantly urothelial, some bladder cancer and upper tract urothelial cancer (BC/UTUC) harbor histologic variants. Small cell BC (SCBC) variants comprised ˜5% of The Cancer Genome Atlas BC cohort, with a poor prognosis. We describe genomic profiles of BC/UTUC with small cell/neuroendocrine features identified in the Foundation Medicine database from June 2012 to September 2018. Of 3368 BC/UTUC samples, 3.92% (132) harbored small cell/neuroendocrine features by immunohistochemistry. Mutations were noted in: TP53 (92%), RB1 (75%), combined TP53/RB1 (72%), and TERT promoter (68%). Of the samples, 6.5% had TMB ≥ 10 mutations/Mb. RNA expression profiling of 24 pure SCBC and 51 urothelial BC (UBC) muscle-invasive samples evaluated from a separate cohort revealed a large number of differentially expressed genes with suppression of several inflammatory pathways in SCBC compared with UBC. This largest reported SCBC dataset to date confirms enrichment of signatures in SCBC similar to small cell lung cancer and describes unique gene expression compared with UBC. These findings may explain aggressive SCBC phenotype. PATIENT SUMMARY: Small cell bladder cancer (SCBC) is an aggressive subtype that microscopically resembles aggressive small cell lung cancer (SCLC). This study confirms that SCBC shares DNA changes similar to SCLC and that SCBC expresses many genes that urothelial bladder cancer does not, possibly explaining aggressive SCBC activity.
虽然主要为尿路上皮，但一些膀胱癌和上尿路尿路上皮癌（BC/UTUC）具有组织学变异型。小细胞膀胱癌（SCBC）变异型约占癌症基因组图谱（TCGA）BC 队列的 5%，预后较差。我们描述了 2012 年 6 月至 2018 年 9 月在 Foundation Medicine 数据库中发现的具有小细胞/神经内分泌特征的 BC/UTUC 的基因组图谱。在 3368 例 BC/UTUC 样本中，通过免疫组织化学检测，有 3.92%（132 例）具有小细胞/神经内分泌特征。在这些样本中，观察到 TP53（92%）、RB1（75%）、TP53/RB1 联合缺失（72%）和 TERT 启动子突变（68%）。在这些样本中，有 6.5%的肿瘤突变负荷（TMB）≥10 个突变/Mb。从另一个队列评估的 24 例纯 SCBC 和 51 例肌层浸润性尿路上皮膀胱癌（UBC）的 RNA 表达谱显示，与 UBC 相比，SCBC 中有大量差异表达基因，并且几个炎症途径受到抑制。这是迄今为止报道的最大的 SCBC 数据集，证实了 SCBC 中富集的特征与小细胞肺癌相似，并描述了与 UBC 相比 SCBC 独特的基因表达。这些发现可能解释了 SCBC 侵袭性表型。患者总结：小细胞膀胱癌（SCBC）是一种侵袭性亚型，显微镜下类似于侵袭性小细胞肺癌（SCLC）。本研究证实，SCBC 与 SCLC 具有相似的 DNA 变化，并且 SCBC 表达了许多尿路上皮膀胱癌不表达的基因，这可能解释了 SCBC 的侵袭性活性。
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