Identification of a novel PDGFRA point mutation at p.P6L as a potential molecular target of imatinib in an eosinophilia patient showing genetic heterogeneity
| Autor: | Qiuling Wu, Shichun Tu, Yadan Wang, Jianqing Yang, Linghui Xia, Miaomiao Zhao, Yaya Li, Min Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Receptor Platelet-Derived Growth Factor alpha Oncogene Proteins Fusion Antineoplastic Agents macromolecular substances PDGFRA Biology Fusion gene Genetic Heterogeneity 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Eosinophilia medicine Humans Point Mutation Pharmacology Bedside to Bench Report Genetic heterogeneity Point mutation Imatinib respiratory system Eosinophil Prognosis digestive system diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Imatinib Mesylate Cancer research Molecular Medicine Biomarker (medicine) medicine.symptom medicine.drug |
| Zdroj: | Cancer Biology & Therapy. 20:402-407 |
| ISSN: | 1555-8576 1538-4047 |
| Popis: | Eosinophilia is a severe disease with increased eosinophil count. The transcript of FIP1L1-PDGFRA fusion gene is a genetic biomarker of clonal eosinophilia screened routinely by reverse transcript PCR (RT-PCR) during diagnosis. Another significant genetic biomarker is the PDGFRA gene alone as some of its mutations are targets of imatinib. In this study, we identified a patient who had typical symptoms of Eosinophilia but had no response to the first-line treatment of hormonotherapy. This patient also showed bone rupture and eosinophil bone infiltration, which are extremely rare among all known eosinophilia patients. We identified the FIP1L1-PDGFRA fusion gene via RT-PCR and Sanger sequencing. Using next generation sequencing (NGS), we detected point mutations in PDGFRA, MYOM2, and ASXL3. The patient then received imatinib therapy, leading to the complete disappearance of FIP1L1-PDGFRA fusion gene and mutated MYOM2. The level of PDGFRA point mutation was also decreased from pre-treatment: 57.86% down to 42.99% at 6 months and to 38.80% at one-year after treatment. The level of ASXL3 mutations did not change significantly. To the best of our knowledge, this is the first case in which the point mutation of PDGFRA has been identified at p.P6L in exon 2, likely making it sensitive to imatinib and thus should be further studied as a potential new molecular target of imatinib therapy. |
| Databáze: | OpenAIRE |
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