Comprehensive molecular profiling of pulmonary pleomorphic carcinoma

Abstract Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We anal...

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Autores principales:	Masaaki Nagano, Shinji Kohsaka, Takuo Hayashi, Toshihide Ueno, Shinya Kojima, Aya Shinozaki-Ushiku, Shigeki Morita, Masumi Tsuda, Shinya Tanaka, Toshiya Shinohara, Yuko Omori, Fumiko Sugaya, Hiroaki Kato, Yoshiaki Narita, Jun Nakajima, Kenji Suzuki, Kazuya Takamochi, Hiroyuki Mano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c6e7bbb8b977426f98a63ff5b8c37c27
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spelling	oai:doaj.org-article:c6e7bbb8b977426f98a63ff5b8c37c272021-12-02T18:02:41ZComprehensive molecular profiling of pulmonary pleomorphic carcinoma10.1038/s41698-021-00201-32397-768Xhttps://doaj.org/article/c6e7bbb8b977426f98a63ff5b8c37c272021-06-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00201-3https://doaj.org/toc/2397-768XAbstract Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.Masaaki NaganoShinji KohsakaTakuo HayashiToshihide UenoShinya KojimaAya Shinozaki-UshikuShigeki MoritaMasumi TsudaShinya TanakaToshiya ShinoharaYuko OmoriFumiko SugayaHiroaki KatoYoshiaki NaritaJun NakajimaKenji SuzukiKazuya TakamochiHiroyuki ManoNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Masaaki Nagano Shinji Kohsaka Takuo Hayashi Toshihide Ueno Shinya Kojima Aya Shinozaki-Ushiku Shigeki Morita Masumi Tsuda Shinya Tanaka Toshiya Shinohara Yuko Omori Fumiko Sugaya Hiroaki Kato Yoshiaki Narita Jun Nakajima Kenji Suzuki Kazuya Takamochi Hiroyuki Mano Comprehensive molecular profiling of pulmonary pleomorphic carcinoma
description	Abstract Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.
format	article
author	Masaaki Nagano Shinji Kohsaka Takuo Hayashi Toshihide Ueno Shinya Kojima Aya Shinozaki-Ushiku Shigeki Morita Masumi Tsuda Shinya Tanaka Toshiya Shinohara Yuko Omori Fumiko Sugaya Hiroaki Kato Yoshiaki Narita Jun Nakajima Kenji Suzuki Kazuya Takamochi Hiroyuki Mano
author_facet	Masaaki Nagano Shinji Kohsaka Takuo Hayashi Toshihide Ueno Shinya Kojima Aya Shinozaki-Ushiku Shigeki Morita Masumi Tsuda Shinya Tanaka Toshiya Shinohara Yuko Omori Fumiko Sugaya Hiroaki Kato Yoshiaki Narita Jun Nakajima Kenji Suzuki Kazuya Takamochi Hiroyuki Mano
author_sort	Masaaki Nagano
title	Comprehensive molecular profiling of pulmonary pleomorphic carcinoma
title_short	Comprehensive molecular profiling of pulmonary pleomorphic carcinoma
title_full	Comprehensive molecular profiling of pulmonary pleomorphic carcinoma
title_fullStr	Comprehensive molecular profiling of pulmonary pleomorphic carcinoma
title_full_unstemmed	Comprehensive molecular profiling of pulmonary pleomorphic carcinoma
title_sort	comprehensive molecular profiling of pulmonary pleomorphic carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c6e7bbb8b977426f98a63ff5b8c37c27
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Comprehensive molecular profiling of pulmonary pleomorphic carcinoma

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