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Genetic interactions reveal distinct biological and therapeutic implications in breast cancer.
Lin, Cai-Jin; Jin, Xi; Ma, Ding; Chen, Chao; Ou-Yang, Yang; Pei, Yu-Chen; Zhou, Chao-Zheng; Qu, Fei-Lin; Wang, Yun-Jin; Liu, Cheng-Lin; Fan, Lei; Hu, Xin; Shao, Zhi-Ming; Jiang, Yi-Zhou.
Afiliación
  • Lin CJ; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Jin X; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Ma D; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Chen C; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Ou-Yang Y; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Pei YC; Precision Cancer Medical Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • Zhou CZ; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Qu FL; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Wang YJ; Precision Cancer Medical Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • Liu CL; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Fan L; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Hu X; Precision Cancer Medical Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: xinhu@fudan.edu.cn.
  • Shao ZM; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: zhimingshao@fudan.edu.cn.
  • Jiang YZ; Key Laboratory of Breast Cancer, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: yizhoujiang@fudan.edu.cn.
Cancer Cell ; 42(4): 701-719.e12, 2024 Apr 08.
Article en En | MEDLINE | ID: mdl-38593782
ABSTRACT
Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Límite: Female / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Límite: Female / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos