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利用全基因组测序建立一种新型恶性腹膜间皮瘤细胞系TU-MM-1并进行突变分析。

Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1, using whole genome sequencing.

作者信息

Oumi Nao, Itamochi Hiroaki, Komatsu Hiroaki, Oishi Tetsuro, Shimada Muneaki, Sato Shinya, Chikumi Jun, Sato Seiya, Nonaka Michiko, Kudoh Akiko, Harada Tasuku

机构信息

Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago, Tottori, 683-8504, Japan.

出版信息

Hum Cell. 2016 Jan;29(1):46-51. doi: 10.1007/s13577-015-0120-8. Epub 2015 Jun 13.

DOI:10.1007/s13577-015-0120-8
PMID:26070481
Abstract

A new cell line of human malignant peritoneal mesothelioma (MPM), TU-MM-1, was established and characterized. The cells showed polygonal morphology, grew in monolayers without contact inhibition and were arranged like a jigsaw puzzle. The chromosome numbers ranged from 41 to 44. A low rate of proliferation was observed and the doubling time was 67.9 h. Genomic DNA sequencing revealed that TU-MM-1 cells harbored missense mutations in APC, LATS2, BRCA1/2, and TP53, and mutation of a splice donor site in BAP1 and loss of CDKN2A gene. We observed the absence of BAP1 and p16(INK4a) proteins, underexpression of LATS2 protein, and overexpression of p53 protein in TU-MM-1 cells in western blot analysis. Heterotransplantation to nude mice produced tumors that had the characteristics of the original tumor. This cell line may be useful for studying biological properties and contribute to novel treatment strategies.

摘要

建立并鉴定了一种新的人恶性腹膜间皮瘤(MPM)细胞系TU-MM-1。这些细胞呈多边形形态,单层生长且无接触抑制,排列如拼图。染色体数目在41至44之间。观察到增殖率较低,倍增时间为67.9小时。基因组DNA测序显示,TU-MM-1细胞在APC、LATS2、BRCA1/2和TP53中存在错义突变,BAP1的剪接供体位点发生突变且CDKN2A基因缺失。在蛋白质印迹分析中,我们观察到TU-MM-1细胞中不存在BAP1和p16(INK4a)蛋白,LATS2蛋白表达不足,p53蛋白过表达。异种移植到裸鼠体内产生了具有原始肿瘤特征的肿瘤。该细胞系可能有助于研究生物学特性,并为新的治疗策略做出贡献。

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引用本文的文献

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Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma.全外显子组测序揭示恶性胸膜间皮瘤中 BAP1、NF2、CDKN2A 和 CUL1 的频繁基因突变。
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The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma.恶性胸膜间皮瘤中,核去泛素化酶 BAP1 通常因体细胞突变和 3p21.1 缺失而失活。
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LATS2 is a tumor suppressor gene of malignant mesothelioma.LATS2 是恶性间皮瘤的肿瘤抑制基因。
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