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Status: Bibliographieeintrag

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Verfasst von:Ugurel, Selma [VerfasserIn]   i
 Gast, Andreas [VerfasserIn]   i
 Sucker, Antje [VerfasserIn]   i
 Rittgen, Werner [VerfasserIn]   i
 Hemminki, Kari [VerfasserIn]   i
 Kumar, Rajiv [VerfasserIn]   i
 Schadendorf, Dirk [VerfasserIn]   i
Titel:B-RAF and N-RAS mutations are preserved during short time in vitro propagation and differentially impact prognosis
Verf.angabe:Selma Ugurel, Ranjit K. Thirumaran, Sandra Bloethner, Andreas Gast, Antje Sucker, Jan Mueller-Berghaus, Werner Rittgen, Kari Hemminki, Jürgen C. Becker, Rajiv Kumar, Dirk Schadendorf
E-Jahr:2007
Jahr:February 21, 2007
Umfang:13 S.
Fussnoten:Gesehen am 05.02.2021
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2007
Band/Heft Quelle:2(2007,2) Artikel-Nummer e236, 13 Seiten
ISSN Quelle:1932-6203
Abstract:In melanoma, the RAS/RAF/MEK/ERK signalling pathway is an area of great interest, because it regulates tumor cell proliferation and survival. A varying mutation rate has been reported for B-RAF and N-RAS, which has been largely attributed to the differential source of tumor DNA analyzed, e.g., fixed tumor tissues or in vitro propagated melanoma cells. Notably, this variation also interfered with interpreting the impact of these mutations on the clinical course of the disease. Consequently, we investigated the mutational profile of B-RAF and N-RAS in biopsies and corresponding cell lines from metastatic tumor lesions of 109 melanoma patients (AJCC stage III/IV), and its respective impact on survival. 97 tissue biopsies and 105 biopsy-derived cell lines were screened for B-RAF and N-RAS mutations by PCR single strand conformation polymorphism and DNA sequencing. Mutations were correlated with patient survival data obtained within a median follow-up time of 31 months. B-RAF mutations were detected in 55% tissues and 51% cell lines, N-RAS mutations in 23% tissues and 25% cell lines, respectively. There was strong concordance between the mutational status of tissues and corresponding cell lines, showing a differing status for B-RAF in only 5% and N-RAS in only 6%, respectively. Patients with tumors carrying mutated B-RAF showed an impaired median survival (8.0 versus 11.8 months, p = 0.055, tissues; 7.1 versus 9.3 months, p = 0.068, cell lines), whereas patients with N-RAS-mutated tumors presented with a favorable prognosis (median survival 12.5 versus 7.9 months, p = 0.084, tissues; 15.4 versus 6.8 months, p = 0.0008, cell lines), each in comparison with wildtype gene status. Multivariate analysis qualified N-RAS (p = 0.006) but not B-RAF mutation status as an independent prognostic factor of overall survival. Our findings demonstrate that B-RAF and N-RAS mutations are well preserved during short term in vitro propagation and, most importantly, differentially impact the outcome of melanoma patients.
DOI:doi:10.1371/journal.pone.0000236
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1371/journal.pone.0000236
 Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0000236
 DOI: https://doi.org/10.1371/journal.pone.0000236
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Biopsy
 Cancers and neoplasms
 Cutaneous melanoma
 Melanoma
 Melanoma cells
 Metastasis
 Mutation
 Mutation detection
K10plus-PPN:174756480X
Verknüpfungen:→ Zeitschrift

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