RET rearrangements are actionable alterations in breast cancer
| Autor: | Bhavna S. Paratala, Jon H. Chung, Casey B. Williams, Bahar Yilmazel, Whitney Petrosky, Kirstin Williams, Alexa B. Schrock, Laurie M. Gay, Ellen Lee, Sonia C. Dolfi, Kien Pham, Stephanie Lin, Ming Yao, Atul Kulkarni, Frances DiClemente, Chen Liu, Lorna Rodriguez-Rodriguez, Shridar Ganesan, Jeffrey S. Ross, Siraj M. Ali, Brian Leyland-Jones, Kim M. Hirshfield |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncogene Proteins Fusion Oncogene Proteins endocrine system diseases Pyridines Receptor ErbB-2 General Physics and Astronomy Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound 0302 clinical medicine Piperidines Medicine Missense mutation Anilides lcsh:Science Regulation of gene expression Multidisciplinary Kinase Metastatic breast cancer 3. Good health Gene Expression Regulation Neoplastic Cell Transformation Neoplastic 030220 oncology & carcinogenesis MCF-7 Cells Female ras Guanine Nucleotide Exchange Factors Mitogen-Activated Protein Kinases Signal Transduction congenital hereditary and neonatal diseases and abnormalities endocrine system Cabozantinib Science Nuclear Receptor Coactivators Mice Nude Antineoplastic Agents Breast Neoplasms Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Breast cancer Cell Line Tumor Animals Humans neoplasms PI3K/AKT/mTOR pathway business.industry Proto-Oncogene Proteins c-ret General Chemistry medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology chemistry NIH 3T3 Cells Quinazolines Cancer research lcsh:Q business |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Fusions involving the oncogenic gene RET have been observed in thyroid and lung cancers. Here we report RET gene alterations, including amplification, missense mutations, known fusions, novel fusions, and rearrangements in breast cancer. Their frequency, oncogenic potential, and actionability in breast cancer are described. Two out of eight RET fusions (NCOA4-RET and a novel RASGEF1A-RET fusion) and RET amplification were functionally characterized and shown to activate RET kinase and drive signaling through MAPK and PI3K pathways. These fusions and RET amplification can induce transformation of non-tumorigenic cells, support xenograft tumor formation, and render sensitivity to RET inhibition. An index case of metastatic breast cancer progressing on HER2-targeted therapy was found to have the NCOA4-RET fusion. Subsequent treatment with the RET inhibitor cabozantinib led to a rapid clinical and radiographic response. RET alterations, identified by genomic profiling, are promising therapeutic targets and are present in a subset of breast cancers. Fusions of the gene RET have been described in thyroid and lung cancers. Here, the AUs identify RET gene alterations, including known fusions, novel fusions, and rearrangements in breast cancer (BC) that are involved in the tumorigenic process and show the benefit of RET therapy in a recurrent BC patient carrying the NCOA4-RET fusion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|