Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ugurel, S; Houben, R; Schrama, D; Voigt, H; Zapatka, M; Schadendorf, D; Brocker, EB; Becker, JC.
Microphthalmia-associated transcription factor gene amplification in metastatic melanoma is a prognostic marker for patient survival, but not a predictive marker for chemosensitivity and chemotherapy response.
Clin Cancer Res. 2007; 13(21):6344-6350
Doi: 10.1158/1078-0432.CCR-06-2682
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- Führende Autor*innen der Med Uni Graz
- Becker Jürgen Christian
- Ugurel-Becker Selma
- Co-Autor*innen der Med Uni Graz
- Schrama David
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- Abstract:
- Purpose: The microphthalmia-associated transcription factor (MITF) is regarded as a key oncogene of the melanocytic lineage since it was detected by a genome-wide analysis to be strongly amplified in 15% to 20% of metastatic melanomas. MITF gene amplification was shown to be associated with a reduced survival in metastatic melanoma patients, and reduction of MITF activity was shown to sensitize melanoma cell lines to chemotherapeutics, suggesting the intratumoral MITF gene copy number as a predictive biomarker of response and survival after chemotherapy. Patients and Methods: To validate this hypothesis, we investigated MITF gene amplification in tumor tissues obtained from 116 metastatic melanoma patients before an individualized sensitivity-directed chemotherapy using quantitative real-time PCR. MITF amplification rates were correlated with tumor chemosensitivity quantified by an ATP-based luminescence assay and with chemotherapy outcome in terms of response and survival. Results: Of 116 tumor tissues, 104 were evaluable for MITF gene amplification. Strong amplification (>= 4 copies per cell) was detected in 24 of 104 tissues (23%), whereas 62 of 104 tissues (60%) harbored >3 copies per cell. Strong MITF gene amplification was associated with a reduced disease-specific survival (P = 0.031). However, no correlation was found between MITF copy number and in vitro chemosensitivity or in vivo chemotherapy response. Conclusion: Our findings suggest that strong amplifications of the melanoma oncogene MITF affects patient survival but does not influence tumor chemosensitivity and chemotherapy response. Thus, the MITF gene copy number seems a useful prognostic marker in metastatic melanoma but could not be confirmed as a predictive marker of chemosensitivity and chemotherapy response.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Aged, 80 and over -
- Antineoplastic Agents - pharmacology
- Female -
- Gene Amplification -
- Gene Expression Profiling -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Male -
- Melanoma - metabolism Melanoma - pathology
- Microphthalmia-Associated Transcription Factor - biosynthesis Microphthalmia-Associated Transcription Factor - genetics
- Middle Aged -
- Prognosis -
- Treatment Outcome -
- Tumor Markers, Biological -