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Aktuelle Dermatologie 2017; 43(01/02): 46-59
DOI: 10.1055/s-0042-116033
DOI: 10.1055/s-0042-116033
Fort- und Weiterbildung
Aktuelle molekulare Diagnostik beim malignen Melanom
Current Molecular Diagnostics in MelanomaWeitere Informationen
Publikationsverlauf
Publikationsdatum:
14. Februar 2017 (online)

Durch den Einsatz neuer Sequenzierungstechniken ist es zu einer rasanten Entwicklung bzgl. der Identifikation von genetischen Varianten beim malignen Melanom gekommen. Die dabei gewonnenen neuen Erkenntnisse erlauben ein besseres Verständnis der Pathogenese des malignen Melanoms und der genetischen Mechanismen der sekundären Behandlungsresistenz
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Literatur
- 1 Davies H, Bignell GR, Cox C. et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 1-13
- 2 Hersey P, Bastholt L, Chiarion-Sileni V. et al. Small molecules and targeted therapies in distant metastatic disease. Ann Oncol 2009; (Suppl. 06) vi35-40
- 3 Sullivan RJ, Flaherty KT. New strategies in melanoma: entering the era of combinatorial therapy. Clin Cancer Res 2015; 21: 2424-2435
- 4 Schadendorf D, Fisher DE, Garbe C. et al. Melanoma. Nature Rev Dis Primers 2015; 1: 1-20
- 5 McArthur GA, Chapman PB, Robert C. et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol 2014; 15: 323-332
- 6 Klein O, Clements A, Menzies AM. et al. BRAF inhibitor activity in V600R metastatic melanoma. Eur J Cancer 2013; 49: 1073-1079
- 7 Gentilcore G, Madonna G, Mozzillo N. et al. Effect of dabrafenib on melanoma cell lines harbouring the BRAF(V600D/R) mutations. BMC Cancer 2013; 13: 17
- 8 Larkin J, Ascierto PA, Dréno B. et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014; 371: 1867-1876
- 9 Long GV, Stroyakovskiy D, Gogas H. et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet 2015; 386: 444-451
- 10 Robert C, Karaszewska B, Schachter J. et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015; 372: 30-39
- 11 Thota R, Johnson DB, Sosman JA. Trametinib in the treatment of melanoma. Expert Opin Biol Ther 2015; 15: 735-747
- 12 Krauthammer M, Kong Y, Ha BH. et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 2012; 44: 1006-1014
- 13 Hodis E, Watson IR, Kryukov GV. et al. A landscape of driver mutations in melanoma. Cell 2012; 150: 251-263
- 14 Cancer Genome Atlas Network. Genomic Classification of Cutaneous Melanoma. Cell 2015; 161: 1681-1696
- 15 Grob JJ, Long GV, Schadendorf D. et al. Disease kinetics for decision-making in advanced melanoma: a call for scenario-driven strategy trials. Lancet Oncol 2015; 16: e522-526
- 16 Ascierto PA, Marincola FM. Atkins MB. What’s new in melanoma?. Combination! J Transl Med 2015; 13: 213
- 17 Metzker ML. Sequencing technologies – the next generation. Nat Rev Genet 2010; 11: 31-46
- 18 Rizzo JM, Buck MJ. Key principles and clinical applications of “next-generation” DNA sequencing. Cancer Prev Res (Phila) 2012; 5: 887-900
- 19 Pleasance ED, Cheetham RK, Stephens PJ. et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010; 463: 191-196
- 20 Prickett TD, Agrawal NS, Wei X. et al. Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet 2009; 41: 1127-1132
- 21 Wei X, Walia V, Lin JC. et al. Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 2011; 43: 442-446
- 22 Prickett TD, Wei X, Cardenas-Navia I. et al. Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma. Nat Genet 2011; 43: 1119-1126
- 23 Johnson DB, Menzies AM, Zimmer L. et al. Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms. Eur J Cancer 2015; 51: 2792-2799
- 24 Manca A, Lissia A, Cossu A. et al. Mutations in ERBB4 may have a minor role in melanoma pathogenesis. J Invest Dermatol 2013; 133: 1685-1687
- 25 Berger MF, Hodis E, Heffernan TP. et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 2012; 485: 502-506
- 26 Zhang T, Dutton-Regester K, Brown KM. et al. The genomic landscape of cutaneous melanoma. Pigment Cell Melanoma Res 2016; 29: 266-283
- 27 Horn S, Figl A, Rachakonda PS. et al. TERT promoter mutations in familial and sporadic melanoma. Science 2013; 339: 959-961
- 28 Akincilar SC, Unal B, Tergaonkar V. Reactivation of telomerase in cancer. Cell Mol Life Sci 2016; 73: 1659-1670
- 29 Shain AH, Yeh I, Kovalyshyn I. et al. The Genetic Evolution of Melanoma from Precursor Lesions. N Engl J Med 2015; 373: 1926-1936
- 30 Greuber EK, Smith-Pearson P, Wang J. et al. Role of ABL family kinases in cancer: from leukaemia to solid tumours. Nat Rev Cancer 2013; 13: 559-571
- 31 Bunting SF, Nussenzweig A. End-joining, translocations and cancer. Nat Rev Cancer 2013; 13: 443-454
- 32 Mertens F, Johansson B, Fioretos T. et al. The emerging complexity of gene fusions in cancer. Nat Rev Cancer 2015; 15: 371-381
- 33 Berger MF, Levin JZ, Vijayendran K. et al. Integrative analysis of the melanoma transcriptome. Genome Res 2010; 20: 413-427
- 34 Wiesner T, He J, Yelensky R. et al. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun 2014; 5: 3116
- 35 Hutchinson KE, Lipson D, Stephens PJ. et al. BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition. Clin Cancer Res 2013; 19: 6696-6702
- 36 Cheng S, Koch WH, Wu L. Co-development of a companion diagnostic for targeted cancer therapy. N Biotechnol 2012; 29: 682-688
- 37 Janku F, Claes B, Huang HJ. et al. BRAF mutation testing with a rapid, fully integrated molecular diagnostics system. Oncotarget 2015; 6: 26886-26894
- 38 Chang GA, Polsky D. Mutational Heterogeneity in Melanoma: An Inconvenient Truth. J Invest Dermatol 2015; 135: 2913-2918
- 39 Riveiro-Falkenbach E, Villanueva CA, Garrido MC. et al. Intra- and Inter-Tumoral Homogeneity of BRAF(V600E) Mutations in Melanoma Tumors. J Invest Dermatol 2015; 135: 3078-3085
- 40 Ilie M, Long-Mira E, Funck-Brentano E. et al. Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma. J Am Acad Dermatol 2015; 72: 786-793
- 41 Just PA, Pouliquen C, Audebourg A. et al. High specificity and sensitivity of NRAS Q61R immunohistochemistry (IHC) in melanomas. J Am Acad Dermatol 2016; 74: 572-573
- 42 Van Allen EM, Wagle N, Sucker A. Dermatologic Cooperative Oncology Group of Germany (DeCOG). et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014; 4: 94-109
- 43 Shi H, Hugo W, Kong X. et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 2014; 4: 80-93
- 44 Moriceau G, Hugo W, Hong A. et al. Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction. Cancer Cell 2015; 27: 240-256
- 45 Johannessen CM, Johnson LA, Piccioni F. et al. A melanocyte lineage program confers resistance to MAP kinase pathway inhibition. Nature 2013; 504: 138-142
- 46 Konieczkowski DJ, Johannessen CM, Abudayyeh O. et al. A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. Cancer Discov 2014; 4: 816-827
- 47 Müller J, Krijgsman O, Tsoi J. et al. Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma. Nat Commun 2014; 5: 5712
- 48 Aparicio S, Caldas C. The implications of clonal genome evolution for cancer medicine. N Engl J Med 2013; 368: 842-851
- 49 Gerlinger M, Rowan AJ, Horswell S. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883-892
- 50 Diaz Jr LA, Williams RT, Wu J. et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012; 486: 537-540
- 51 Obenauf AC, Zou Y, Ji AL. et al. Therapy-induced tumour secretomes promote resistance and tumour progression. Nature 2015; 520: 368-372
- 52 Waclaw B, Bozic I, Pittman ME. et al. A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity. Nature 2015; 525: 261-264
- 53 McGranahan N, Favero F, de Bruin EC. et al. Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci Transl Med 2015; 7: 283ra54
- 54 Held MA, Langdon CG, Platt JT. et al. Genotype-selective combination therapies for melanoma identified by high-throughput drug screening. Cancer Discov 2013; 3: 52-67
- 55 Gawad C, Koh W, Quake SR. Single-cell genome sequencing: current state of the science. Nat Rev Genet 2016; 17: 175-188
- 56 Patel AP, Tirosh I, Trombetta JJ. et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014; 344: 1396-1401
- 57 Suzuki A, Matsushima K, Makinoshima H. et al. Single-cell analysis of lung adenocarcinoma cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment. Genome Biol 2015; 16: 66
- 58 Ennen M, Keime C, Kobi D. et al. Single-cell gene expression signatures reveal melanoma cell heterogeneity. Oncogene 2015; 34: 3251-3263
- 59 Hou Y, Wu K, Shi X. et al. Comparison of variations detection between whole-genome amplification methods used in single-cell resequencing. Gigascience 2015; 4: 37
- 60 Van Allen EM, Miao D, Schilling B. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 2015; 9; 350: 207-211
- 61 Hugo W, Zaretsky JM, Sun L. et al. Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma. Cell 2016; 165: 35-44
- 62 Johnson DB, Frampton GM, Rioth MJ. et al. Hybrid capture-based next-generation sequencing (HC NGS) in melanoma to identify markers of response to anti-PD-1/PD-L1. J Clin Oncol 2016 34. (suppl; abstr 105)