Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma

Abstract The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations w...
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Autor*in:	Ruiying Zhao [verfasserIn] Yunhua Xu [verfasserIn] Yedan Chen [verfasserIn] Jiajun Zhang [verfasserIn] Fei Teng [verfasserIn] Sha Liao [verfasserIn] Shengnan Chen [verfasserIn] Qian Wu [verfasserIn] Chan Xiang [verfasserIn] Jiaohui Pang [verfasserIn] Zhanxian Shang [verfasserIn] Jikai Zhao [verfasserIn] Hairong Bao [verfasserIn] Hua Bao [verfasserIn] Yang Shao [verfasserIn] Shun Lu [verfasserIn] Yuchen Han [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: npj Precision Oncology - Nature Portfolio, 2017, 7(2023), 1, Seite 14
Übergeordnetes Werk:	volume:7 ; year:2023 ; number:1 ; pages:14

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41698-023-00430-8

Katalog-ID:	DOAJ093335814

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callnumber-first	R - Medicine
author	Ruiying Zhao
spellingShingle	Ruiying Zhao misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
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topic_title	RC254-282 Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
topic	misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
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title_full	Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
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author_browse	Ruiying Zhao Yunhua Xu Yedan Chen Jiajun Zhang Fei Teng Sha Liao Shengnan Chen Qian Wu Chan Xiang Jiaohui Pang Zhanxian Shang Jikai Zhao Hairong Bao Hua Bao Yang Shao Shun Lu Yuchen Han
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title_sort	clonal dynamics and stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
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title_auth	Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
abstract	Abstract The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.
abstractGer	Abstract The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.
abstract_unstemmed	Abstract The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.
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title_short	Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma
url	https://doi.org/10.1038/s41698-023-00430-8 https://doaj.org/article/14d126bb6dbe4633a90db4a01c61c1aa https://doaj.org/toc/2397-768X
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author2	Yunhua Xu Yedan Chen Jiajun Zhang Fei Teng Sha Liao Shengnan Chen Qian Wu Chan Xiang Jiaohui Pang Zhanxian Shang Jikai Zhao Hairong Bao Hua Bao Yang Shao Shun Lu Yuchen Han
author2Str	Yunhua Xu Yedan Chen Jiajun Zhang Fei Teng Sha Liao Shengnan Chen Qian Wu Chan Xiang Jiaohui Pang Zhanxian Shang Jikai Zhao Hairong Bao Hua Bao Yang Shao Shun Lu Yuchen Han
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doi_str	10.1038/s41698-023-00430-8
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up_date	2024-07-03T16:42:46.312Z
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Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma

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