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Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer

KRAS mutations are associated with tumor resistance to EGFR TKIs (erlotinib, gefitinib) and to monoclonal antibody against EGFR (cetuximab). Targeted treatment of mutated RAS patients is still considered as a challenge. Inhibitors of c-Met (onartuzumab or tiwantinib) and MEK (selumetinib—a dual inhi...

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Autores principales: Nicoś, Marcin, Krawczyk, Paweł, Jarosz, Bożena, Sawicki, Marek, Szumiłło, Justyna, Trojanowski, Tomasz, Milanowski, Janusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844634/
https://www.ncbi.nlm.nih.gov/pubmed/25902737
http://dx.doi.org/10.1007/s10238-015-0349-2
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author Nicoś, Marcin
Krawczyk, Paweł
Jarosz, Bożena
Sawicki, Marek
Szumiłło, Justyna
Trojanowski, Tomasz
Milanowski, Janusz
author_facet Nicoś, Marcin
Krawczyk, Paweł
Jarosz, Bożena
Sawicki, Marek
Szumiłło, Justyna
Trojanowski, Tomasz
Milanowski, Janusz
author_sort Nicoś, Marcin
collection PubMed
description KRAS mutations are associated with tumor resistance to EGFR TKIs (erlotinib, gefitinib) and to monoclonal antibody against EGFR (cetuximab). Targeted treatment of mutated RAS patients is still considered as a challenge. Inhibitors of c-Met (onartuzumab or tiwantinib) and MEK (selumetinib—a dual inhibitor of MEK1 and MEK2) signaling pathways showed activity in patients with mutations in KRAS that can became an effective approach in carriers of such disorders. BRAF mutation is very rare in patients with NSCLC, and its presence is associated with sensitivity of tumor cells to BRAF inhibitors (vemurafenib, dabrafenib). In the present study, the frequency and type of KRAS and BRAF mutation were assessed in 145 FFPE tissue samples from CNS metastases of NSCLC. In 30 patients, material from the primary tumor was simultaneously available. Real-time PCR technique with allele-specific molecular probe (KRAS/BRAF Mutation Analysis Kit, Entrogen, USA) was used for molecular tests. KRAS mutations were detected in 21.4 % of CNS metastatic lesions and in 23.3 % of corresponding primary tumors. Five mutations were identified both in primary and in metastatic lesions, while one mutation only in primary tumor and one mutation only in the metastatic tumor. Most of mutations were observed in codon 12 of KRAS; however, an individual patient had diagnosed a rare G13D and Q61R substitutions. KRAS mutations were significantly more frequent in adenocarcinoma patients and smokers. Additional analysis indicated one patient with rare coexistence of KRAS and DDR2 mutations. BRAF mutation was not detected in the examined materials. KRAS frequency appears to be similar in primary and CNS.
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spelling pubmed-48446342016-05-21 Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer Nicoś, Marcin Krawczyk, Paweł Jarosz, Bożena Sawicki, Marek Szumiłło, Justyna Trojanowski, Tomasz Milanowski, Janusz Clin Exp Med Original Article KRAS mutations are associated with tumor resistance to EGFR TKIs (erlotinib, gefitinib) and to monoclonal antibody against EGFR (cetuximab). Targeted treatment of mutated RAS patients is still considered as a challenge. Inhibitors of c-Met (onartuzumab or tiwantinib) and MEK (selumetinib—a dual inhibitor of MEK1 and MEK2) signaling pathways showed activity in patients with mutations in KRAS that can became an effective approach in carriers of such disorders. BRAF mutation is very rare in patients with NSCLC, and its presence is associated with sensitivity of tumor cells to BRAF inhibitors (vemurafenib, dabrafenib). In the present study, the frequency and type of KRAS and BRAF mutation were assessed in 145 FFPE tissue samples from CNS metastases of NSCLC. In 30 patients, material from the primary tumor was simultaneously available. Real-time PCR technique with allele-specific molecular probe (KRAS/BRAF Mutation Analysis Kit, Entrogen, USA) was used for molecular tests. KRAS mutations were detected in 21.4 % of CNS metastatic lesions and in 23.3 % of corresponding primary tumors. Five mutations were identified both in primary and in metastatic lesions, while one mutation only in primary tumor and one mutation only in the metastatic tumor. Most of mutations were observed in codon 12 of KRAS; however, an individual patient had diagnosed a rare G13D and Q61R substitutions. KRAS mutations were significantly more frequent in adenocarcinoma patients and smokers. Additional analysis indicated one patient with rare coexistence of KRAS and DDR2 mutations. BRAF mutation was not detected in the examined materials. KRAS frequency appears to be similar in primary and CNS. Springer International Publishing 2015-04-23 2016 /pmc/articles/PMC4844634/ /pubmed/25902737 http://dx.doi.org/10.1007/s10238-015-0349-2 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Nicoś, Marcin
Krawczyk, Paweł
Jarosz, Bożena
Sawicki, Marek
Szumiłło, Justyna
Trojanowski, Tomasz
Milanowski, Janusz
Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer
title Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer
title_full Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer
title_fullStr Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer
title_full_unstemmed Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer
title_short Analysis of KRAS and BRAF genes mutation in the central nervous system metastases of non-small cell lung cancer
title_sort analysis of kras and braf genes mutation in the central nervous system metastases of non-small cell lung cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844634/
https://www.ncbi.nlm.nih.gov/pubmed/25902737
http://dx.doi.org/10.1007/s10238-015-0349-2
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