Detection of EGFR, KRAS and BRAF mutations in metastatic cells from cerebrospinal fluid
| Autor: | Julien Guinde, Isabelle Nanni-Metellus, Diane Frankel, Philippe Astoul, Elise Kaspi, L'Houcine Ouafik, Pascale Tomasini, Florent Amatore, Véronique Secq, Andrée Robaglia-Schlupp, Patrice Roll, Fabrice Barlesi |
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| Přispěvatelé: | Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Oncologie multidisciplinaire et innovations thérapeutiques [Hôpital Nord - APHM], Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division d'oncologie thoracique, Département des maladies pulmonaires, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), service hospitalier d'anatomie et cytologie pathologique humaine, APHM, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Proto-Oncogene Proteins B-raf Lung Neoplasms Clinical Biochemistry Viral Oncogene Adenocarcinoma of Lung [SDV.CAN]Life Sciences [q-bio]/Cancer medicine.disease_cause Proto-Oncogene Proteins p21(ras) 03 medical and health sciences symbols.namesake 0302 clinical medicine medicine Humans Epidermal growth factor receptor ComputingMilieux_MISCELLANEOUS Aged Sanger sequencing biology business.industry Biochemistry (medical) General Medicine Middle Aged medicine.disease 3. Good health ErbB Receptors 030104 developmental biology Real-time polymerase chain reaction 030220 oncology & carcinogenesis Cancer cell Mutation Cancer research Mutation testing biology.protein symbols Adenocarcinoma Female KRAS business |
| Zdroj: | Clinical Chemistry and Laboratory Medicine Clinical Chemistry and Laboratory Medicine, De Gruyter, 2018, 56 (5), pp.748-753. ⟨10.1515/cclm-2017-0527⟩ |
| ISSN: | 1434-6621 1437-4331 |
| DOI: | 10.1515/cclm-2017-0527⟩ |
| Popis: | Background:In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed.Methods:We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF.Results:Five patients showed mutations in one or two actionable genes, two harboured anEGFRmutation (exons 19 and 21), one only aKRASmutation, one bothEGFRandKRASmutations and one aBRAFmutation. In all cases, the results of mutation testing provided new major information for patient management, leading to therapeutic adaptation. CSF molecular analysis identified mutations not detected in other neoplastic sites for two patients. In one case, the EGFR p.Thr790Met was identified. CSF was also the only sample available for genetic testing for almost all patients at the time of disease progression.Conclusions:When cancer cells are present in the CSF, the molecular profiling from the cell pellets is relevant, as it can detect supplemental or different mutations compared to a previous analysis of the primitive tumour or plasma cell-free DNA and allows the adaptation of the treatment strategy. |
| Databáze: | OpenAIRE |
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