@article{SchartlShenMaurusetal.2015,
  author    = {Schartl, Manfred and Shen, Yingjia and Maurus, Katja and Walter, Ron and Tomlinson, Chad and Wilson, Richard K. and Postlethwait, John and Warren, Wesley C.},
  title     = {Whole body melanoma transcriptome response in medaka},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0143057},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144714},
  pages     = {e0143057},
  year      = {2015},
  abstract  = {The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model.},
  language  = {en}
}
@article{MaurusKosnopfelKneitzetal.2022,
  author    = {Maurus, K. and Kosnopfel, C. and Kneitz, H. and Appenzeller, S. and Schrama, D. and Glutsch, V. and Roth, S. and Gerhard-Hartmann, E. and Rosenfeldt, M. and M{\"o}hrmann, L. and Fr{\"o}hlich, M. and H{\"u}bschmann, D. and Stenzinger, A. and Glimm, H. and Fr{\"o}hling, S. and Goebeler, M. and Rosenwald, A. and Kutzner, H. and Schilling, B.},
  title     = {Cutaneous epithelioid haemangiomas show somatic mutations in the mitogen-activated protein kinase pathway},
  series = {British Journal of Dermatology},
  volume    = {186},
  journal   = {British Journal of Dermatology},
  number    = {3},
  doi       = {10.1111/bjd.20869},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258333},
  pages     = {553-563},
  year      = {2022},
  abstract  = {Background Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently recurs after resection. So far, the underlying pathogenesis is largely elusive. Objectives To identify genetic alterations by next-generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH. Methods DNA and RNA from an EH lesion of an index patient were subjected to whole-genome and RNA sequencing. Multiplex PCR-based panel sequencing of genomic DNA isolated from archival formalin-fixed paraffin-embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations. Results We identified somatic mutations in genes of the mitogen-activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low-frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells. Conclusions Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.},
  language  = {en}
}