BRAF V600E mutation is a potential therapeutic target for a small subset of synovial sarcoma
| Autor: | Takuji Seo, Shun-ichi Watanabe, Sho Watanabe, Hitoshi Ichikawa, Akira Kawai, Kenji Tamura, Akihiko Yoshida, Noboru Yamamoto, Masaya Sekimizu, Akihiko Shimomura, Takashi Kohno, Takashi Kubo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Proto-Oncogene Proteins B-raf 0301 basic medicine Neuroblastoma RAS viral oncogene homolog Pathology medicine.medical_specialty Combination therapy MAP Kinase Signaling System Mediastinal Neoplasms Pathology and Forensic Medicine Sarcoma Synovial Young Adult 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor medicine Humans Phosphorylation Protein Kinase Inhibitors Trametinib business.industry Dabrafenib medicine.disease Synovial sarcoma 030104 developmental biology 030220 oncology & carcinogenesis Mutation Mutation (genetic algorithm) Cancer research Immunohistochemistry Female Sarcoma business medicine.drug |
| Zdroj: | Modern Pathology. 33:1660-1668 |
| ISSN: | 0893-3952 |
| Popis: | Synovial sarcoma (SS) is an aggressive tumor that most often affects the deep soft tissues in young adults. Intrathoracic SS is rare and is associated with poor outcome, highlighting the urgent need for a novel therapeutic strategy. In the process of clinical sequencing, we identified two patients with intrathoracic SS harboring the BRAF V600E mutation. The patients were women aged 32 and 23 years, and both presented with SS18-SSX2-positive monophasic SS in the thoracic cavity. BRAF V600E mutations were detected by next generation sequencing, and validated immunohistochemically by diffuse intense positivity to BRAF V600E mutation-specific antibodies. The phosphorylated ERK (pERK) immunohistochemistry result was also positive. One patient received a combination therapy of dabrafenib and trametinib, which led to tumor shrinkage. However, the tumor growth progressed 7.5 months later with an additional NRAS Q61K mutation. Immunohistochemical screening of 67 archival SS tumor samples failed to identify additional samples with BRAF V600E mutation. However, 32% of BRAF V600E-negative cases was positive for pERK, and one of the six tumors showing the highest pERK expression harbored an FGFR2-activating mutation. This is the first report of targetable BRAF mutation in a small subset of SS. Our study suggests involvement of the mitogen-activated protein kinase pathway and the potential clinical implication of BRAF mutation screening in SS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink