| Autor: |
Papp O; 2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.; Turbine Simulated Cell Technologies, 1027 Budapest, Hungary., Doma V; 2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.; Department of Dermatology, Venerology and Dermato-Oncology, Semmelweis University, 1085 Budapest, Hungary., Gil J; Division of Oncology, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Markó-Varga G; Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, 221 84 Lund, Sweden.; Chemical Genomics Global Research Lab, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.; 1st Department of Surgery, Tokyo Medical University, Tokyo 160-8582, Japan., Kárpáti S; Department of Dermatology, Venerology and Dermato-Oncology, Semmelweis University, 1085 Budapest, Hungary., Tímár J; 2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary., Vízkeleti L; 2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary. |
| Abstrakt: |
Malignant melanoma is one of the most aggressive skin cancers with high potential of visceral dissemination. Since the information about melanoma genomics is mainly based on primary tumors and lymphatic or skin metastases, an autopsy-based visceral metastasis biobank was established. We used copy number variation arrays ( N = 38 samples) to reveal organ specific alterations. Results were partly completed by proteomic analysis. A significant increase of high-copy number gains was found in an organ-specific manner, whereas copy number losses were predominant in brain metastases, including the loss of numerous DNA damage response genes. Amplification of many immune genes was also observed, several of them are novel in melanoma, suggesting that their ectopic expression is possibly underestimated. This "immunogenic mimicry" was exclusive for lung metastasis. We also provided evidence for the possible autocrine activation of c-MET, especially in brain and lung metastases. Furthermore, frequent loss of 9p21 locus in brain metastases may predict higher metastatic potential to this organ. Finally, a significant correlation was observed between BRAF gene copy number and mutant allele frequency, mainly in lung metastases. All of these events may influence therapy efficacy in an organ specific manner, which knowledge may help in alleviating difficulties caused by resistance. |
