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Spatial whole exome sequencing reveals the genetic features of highly-aggressive components in lung adenocarcinoma.
Li, Jianfu; Xiong, Shan; He, Ping; Liang, Peng; Li, Caichen; Zhong, Ran; Cai, Xiuyu; Xie, Zhanhong; Liu, Jun; Cheng, Bo; Chen, Zhuxing; Liang, Hengrui; Lao, Shen; Chen, Zisheng; Shi, Jiang; Li, Feng; Feng, Yi; Huo, Zhenyu; Deng, Hongsheng; Yu, Ziwen; Wang, Haixuan; Zhan, Shuting; Xiang, Yang; Wang, Huiting; Zheng, Yongmin; Lin, Xiaodong; He, Jianxing; Liang, Wenhua.
Afiliación
  • Li J; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Xiong S; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • He P; Department of pathology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Liang P; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Li C; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Zhong R; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Cai X; Department of General Internal Medicine, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.
  • Xie Z; Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou 510120, China.
  • Liu J; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Cheng B; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Chen Z; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Liang H; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Lao S; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Chen Z; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Shi J; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Li F; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Feng Y; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Huo Z; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Deng H; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Yu Z; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Wang H; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Zhan S; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Xiang Y; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Wang H; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Zheng Y; Department of pathology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • Lin X; Department of pathology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China.
  • He J; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China; Southern Medical University, Guangzhou 510120, China
  • Liang W; Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China. Electronic address: liangwh1987@163.com.
Neoplasia ; 54: 101013, 2024 08.
Article en En | MEDLINE | ID: mdl-38850835
ABSTRACT
In invasive lung adenocarcinoma (LUAD), patients with micropapillary (MIP) or solid (SOL) components had a significantly poorer prognosis than those with only lepidic (LEP), acinar (ACI) or papillary (PAP) components. It is interesting to explore the genetic features of different histologic subtypes, especially the highly aggressive components. Based on a cohort of 5,933 patients, this study observed that in different tumor size groups, LUAD with MIP/SOL components showed a different prevalence, and patients with ALK alteration or TP53 mutations had a higher probability of developing MIP/SOL components. To control individual differences, this research used spatial whole-exome sequencing (WES) via laser-capture microdissection of five patients harboring these five coexistent components and identified genetic features among different histologic components of the same tumor. In tracing the evolution of components, we found that titin (TTN) mutation might serve as a crucial intratumor potential driver for MIP/SOL components, which was validated by a cohort of 146 LUAD patients undergoing bulk WES. Functional analysis revealed that TTN mutations enriched the complement and coagulation cascades, which correlated with the pathway of cell adhesion, migration, and proliferation. Collectively, the histologic subtypes of invasive LUAD were genetically different, and certain trunk genotypes might synergize with branching TTN mutation to develop highly aggressive components.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Secuenciación del Exoma / Adenocarcinoma del Pulmón / Neoplasias Pulmonares / Mutación Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Secuenciación del Exoma / Adenocarcinoma del Pulmón / Neoplasias Pulmonares / Mutación Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China