| Autor: |
Lavdovskaia, E.D., Iyevleva, A.G., Sokolenko, A.P., Mitiushkina, N.V., Preobrazhenskaya, E.V., Tiurin, V.I., Ivantsov, A.O., Bizin, I.V., Stelmakh, L.V., Moiseyenko, F.V., Karaseva, N.A., Orlov, S.V., Moiseyenko, V.M., Korzhenevskaya, M.A., Zaitsev, I.A., Kozak, A.R., Chistyakov, I.V., Akopov, A.L., Volkov, N.M., Togo, A.V., Imyanitov, E.N. |
| Rok vydání: |
2018 |
| Předmět: |
|
| DOI: |
10.6084/m9.figshare.7007450.v1 |
| Popis: |
Background: This study evaluated the distribution of epidermal growth factor receptor (EGFR) T790M mutations in treatment-naïve tumor and normal samples obtained from cancer patients. Methods: We utilized allele-specific PCR (AS-PCR), digital droplet PCR (ddPCR) and next generation sequencing (NGS) to detect EGFR T790M allele in several collections of tumor and normal human tissues. Results: AS-PCR analysis of treatment-naïve tumor samples revealed somatic T790M mutation in 3/394 (1%) non-small cell lung carcinomas (NSCLC) carrying the tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutation, but in none of 334 NSCLC lacking EGFR exon 19 deletions (ex19del) or L858R substitutions and in none of 235 non-lung tumors. Use of highly sensitive and quantitative assays, such as ddPCR and NGS, produced a high number of T790M-specific signals even in presumably T790M-negative DNA specimens. This background noise was evidently higher in degraded DNA isolated from formalin-fixed paraffin-embedded tissues as compared to high molecular weight DNA. A combination of AS-PCR, ddPCR and NGS revealed mosaic EGFR T790M allele in 2/68 (3%) NSCLC treated with the first-generation TKI. Both these tumors produced evident and durable response to gefitinib. Conclusion: Detection of mosaic EGFR T790M mutation in treatment-naïve samples may be compromised by yet unresolved technical issues and may have limited clinical value. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
