Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma.
Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma.
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DOI：
10.1002/cam4.4096
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发表时间：
2021-09
期刊：
影响因子：
4
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Xie M;Fu X;Wang W
睾丸中线癌是一种具有t（15，19）易位的侵袭性肿瘤。本文介绍原发性肺NMC的临床病理特征和分子遗传学改变。荧光原位杂交（FISH）检测NUT易位。进行下一代测序（NGS）以研究基因组景观。通过免疫组织化学（IHC）分析回顾性筛选了289例未分化肺癌组织的NUT表达。总共审查了2136例肺癌样本。我们连续确定了12例原发性肺NMC。电脑断层显示位于中央的巨大的肺肿块，同侧纵隔淋巴结和胸膜受累。肿瘤细胞呈弥漫性低分化和局灶性鳞状分化，NUT表达阳性。通过FISH检测证实NUT重排。通过NGS研究了10个NMC样品。最常见的变异是P53、PIK 3CA、AUTS 2、ITIH 2和CDKL 5基因。肺NMC显示PI 3 K/AKT通路活性增加。在筛选研究中，在2例病例中发现了BRD 4 ‐NUT重排。NUT重排仍然是诊断肺NMC的金标准。PI 3 K抑制是肺NMC的潜在靶向治疗。我们报告原发性肺NUT中线癌的临床病理特征和分子遗传学改变。10个NMC样品回顾性地进行了全面的基因组分析（CGP），这表明PI 3 K/AKT途径的活性增加。PI 3 K抑制可能有利于BRD-NUT融合阳性肺NMC。
Pulmonary nuclear protein of the testis (NUT) midline carcinoma (NMC) is a aggressive cancer with t (15, 19) translocation. Here we present the clinicopathological characteristics and molecular genetics alterations of primary pulmonary NMC. Fluorescence in situ hybridization (FISH) assay was performed to evaluate NUT translocation. Next generation sequencing (NGS) was performed to investigate genomic landscape. A panel of 289 lung cancer tissues with undifferentiation was retrospectively screened for NUT expression by immunohistochemical (IHC) assay. Overall, 2136 lung cancer samples were reviewed. We consecutively identified 12 cases of primary pulmonary NMC. Computed tomography revealed centrally located bulky lung mass with ipsilateral mediastinal lymph node and pleural involvements. Tumor cells presented diffuse poor differentiation and focal squamous differentiation with positive NUT expression. NUT rearrangement was confirmed by FISH assay. Ten NMC samples were investigated by NGS. The most common alterations identified were P53, PIK3CA, AUTS2, ITIH2, and CDKL5 genes. Pulmonary NMC exhibited increased activity of PI3K/AKT pathway. In the screening study, BRD4‐NUT rearrangement was identified in two cases. NUT rearrangement remains the gold standard in the diagnosis of pulmonary NMC. PI3K inhibition is a potential targeted therapy for pulmonary NMC. We present the clinicopathological characteristics and molecular genetics alterations of primary pulmonary NUT midline carcinoma (NMC). Ten NMC samples had retrospectively undergone comprehensive genomic profiling (CGP), which revealed increased activity of the PI3K/AKT pathway. PI3K inhibition may be beneficial for BRD‐NUT fusion‐positive pulmonary NMC.
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DOI：
10.1097/jto.0000000000000545
发表时间：
2015-06
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Sholl LM;Nishino M;Pokharel S;Mino-Kenudson M;French CA;Janne PA;Lathan C
通讯作者：
Lathan C
影响因子：
6.2
作者：
Chau NG;Hurwitz S;Mitchell CM;Aserlind A;Grunfeld N;Kaplan L;Hsi P;Bauer DE;Lathan CS;Rodriguez-Galindo C;Tishler RB;Haddad RI;Sallan SE;Bradner JE;French CA
通讯作者：
French CA
影响因子：
5.7
作者：
Sun, Kaiming;Atoyan, Ruzanna;Wang, Jing
通讯作者：
Wang, Jing
影响因子：
5.6
作者：
Haack, Herbert;Johnson, Laura A.;French, Christopher A.
通讯作者：
French, Christopher A.
影响因子：
4.8
作者：
Wang, Ranran;You, Jianxin
通讯作者：
You, Jianxin