Genomic features of bladder neuroendocrine carcinoma with composite histology.

IF 2.5 4区 生物学 Q3 CELL BIOLOGY
Akihiro Ohmoto, Keiichiro Kitahama, Yasuyuki Shigematsu, Naomi Hayashi, Junji Yonese, Kentaro Inamura, Shunji Takahashi
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引用次数: 0

Abstract

Neuroendocrine carcinoma (NEC) is a rare and aggressive malignancy derived from multiple body parts, with the urogenital organs being the second-largest extrapulmonary sites. The detailed mechanism of bladder NEC pathogenesis remains unknown. We reviewed data from 23 patients diagnosed with NEC from urogenital organs (bladder and prostate) and conducted targeted sequencing of 523 cancer-related genes, focusing on bladder NEC. While 14 cases featured a pure NEC histology, the remaining nine cases included NEC histology mixed with other tumors, such as urothelial carcinoma (UC) or adenocarcinoma. Median overall survival in the entire cohort was 11.1 months, and survival curves were comparable between pure NEC and NEC of mixed appearance. Major mutations detected in the NEC component were in TP53 (38%), TERT promoter (31%), PIK3CA (25%), histone-modification genes (19%), and RB1 (19%). The BARD1 frameshift variant related to homologous recombination was also detected in one patient. More than half of the patients had a high total mutational burden (TMB; ≥10), including two with a TMB ≥45. Intriguingly, at least one identical gene variant in driver genes was detected between NEC and non-NEC (UC) components in the four bladder specimens analyzed. These results highlight the possibility of shared genetic background between bladder NEC and UC. Additionally, several cases harbored druggable gene alterations as presented by TMB-high. Our presentation of the histopathological and molecular features of NEC may help clarify the underlying mechanisms and contribute to efficient treatment of the disease.

复合组织学膀胱神经内分泌癌的基因组特征。
神经内分泌癌(NEC)是一种罕见的侵袭性恶性肿瘤,起源于多个身体部位,其中泌尿生殖器官是第二大肺外部位。膀胱NEC发病的具体机制尚不清楚。我们回顾了来自泌尿生殖器官(膀胱和前列腺)诊断为NEC的23例患者的数据,并对523个癌症相关基因进行了靶向测序,重点是膀胱NEC。14例为纯NEC组织学,其余9例包括NEC组织学合并其他肿瘤,如尿路上皮癌(UC)或腺癌。整个队列的中位总生存期为11.1个月,单纯NEC和混合型NEC的生存曲线具有可比性。在NEC成分中检测到的主要突变是TP53(38%)、TERT启动子(31%)、PIK3CA(25%)、组蛋白修饰基因(19%)和RB1(19%)。在1例患者中也检测到与同源重组相关的BARD1移码变异。超过一半的患者有较高的总突变负担(TMB;≥10),其中2例TMB≥45。有趣的是,在分析的四个膀胱标本中,在NEC和非NEC (UC)成分之间检测到驱动基因中至少有一个相同的基因变异。这些结果突出了膀胱NEC和UC之间共享遗传背景的可能性。此外,一些病例存在可药物性基因改变,表现为TMB-high。我们对NEC的组织病理学和分子特征的介绍可能有助于阐明其潜在机制,并有助于有效治疗该疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Histology and histopathology
Histology and histopathology 生物-病理学
CiteScore
3.90
自引率
0.00%
发文量
232
审稿时长
2 months
期刊介绍: HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.
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