PMID- 34409758 OWN - NLM STAT- MEDLINE DCOM- 20220303 LR - 20220303 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 10 IP - 17 DP - 2021 Sep TI - Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma. PG - 5757-5764 LID - 10.1002/cam4.4096 [doi] AB - INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: NUT rearrangement remains the gold standard in the diagnosis of pulmonary NMC. PI3K inhibition is a potential targeted therapy for pulmonary NMC. CI - (c) 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Xie, Mian AU - Xie M AUID- ORCID: 0000-0002-5013-6673 AD - Department of Medical Oncology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. FAU - Fu, Xinge AU - Fu X AD - Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. FAU - Wang, Wei AU - Wang W AD - Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Beijing, China. LA - eng GR - 81672293/National Natural Science Foundation of China/ GR - 81972178/National Natural Science Foundation of China/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210819 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 SB - IM MH - Adult MH - Aged MH - Female MH - High-Throughput Nucleotide Sequencing/*methods MH - Humans MH - Lung Neoplasms/*genetics/pathology MH - Male MH - Middle Aged MH - Young Adult PMC - PMC8419746 OTO - NOTNLM OT - NUT midline carcinoma OT - lung cancer OT - squamous cell carcinoma COIS- None declared. EDAT- 2021/08/20 06:00 MHDA- 2022/03/04 06:00 PMCR- 2021/08/19 CRDT- 2021/08/19 07:10 PHST- 2021/05/24 00:00 [revised] PHST- 2020/11/25 00:00 [received] PHST- 2021/05/29 00:00 [accepted] PHST- 2021/08/20 06:00 [pubmed] PHST- 2022/03/04 06:00 [medline] PHST- 2021/08/19 07:10 [entrez] PHST- 2021/08/19 00:00 [pmc-release] AID - CAM44096 [pii] AID - 10.1002/cam4.4096 [doi] PST - ppublish SO - Cancer Med. 2021 Sep;10(17):5757-5764. doi: 10.1002/cam4.4096. Epub 2021 Aug 19.