Detection of driver mutations in FFPE samples from patients with verified malignant melanoma
| Autor: | Ivana Kasubova, Bibiana Malicherova, Tatiana Péčová, Zora Lasabova, Martina Bobrovska, E. Minarikova, Lukáš Plank, Igor Homola, Tatiana Burjanivova |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Proto-Oncogene Proteins B-raf
rac1 GTP-Binding Protein Slovakia Cancer Research medicine.medical_treatment DNA Mutational Analysis Protein Serine-Threonine Kinases medicine.disease_cause Polymerase Chain Reaction law.invention Targeted therapy Metastasis 03 medical and health sciences symbols.namesake 0302 clinical medicine law Phosphoprotein Phosphatases Humans Medicine Melanoma neoplasms Polymerase chain reaction Sanger sequencing Mutation Paraffin Embedding business.industry Nuclear Proteins Immunotherapy medicine.disease Oncology 030220 oncology & carcinogenesis symbols Cancer research business Carcinogenesis |
| Zdroj: | Neoplasma. 66:33-38 |
| ISSN: | 1338-4317 |
| Popis: | Malignant melanoma is an oncological disease characterized by etiologic heterogeneity and it has increasing incidence and mortality in the Slovak Republic. While it is treated surgically in combination with chemotherapy, targeted therapy, and immunotherapy, malignant melanomas can ulcerate and are susceptible to infections. These are highly aggressive cancers with metastasis, and recent studies have shown the presence of mutations in RAC1, PPP6C and STK19 genes in melanoma patients. Mutations in these genes are driver mutations; important in oncogenesis and providing selective advantage to tumor cells. The aim of our study is to establish a method to detect driver mutations in formalin-fixed, paraffin embedded (FFPE) tissue DNA. We applied Sanger sequencing to detect driver somatic mutations in RAC1, PPP6C, STK19 and BRAF genes in patients with malignant melanoma. Confirmation of BRAF V600E mutation was obtained by allele-specific PCR. The BRAF V600E mutation was present in 15 of 113 patients (13.2%) and the driver mutation in 7 of 113 patients (6.2 %). Our results demonstrate that Sanger sequencing analysis detects mutations in FFPE clinical samples. The identification of these somatic driver mutations in samples with verified malignant melanomas enabled development of a molecular classification of melanomas, and our study provides evidence of diversity of novel driver mutations implicated in malignant melanoma pathogenesis. These findings could have very important implications for targeted therapy. |
| Databáze: | OpenAIRE |
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