piwik-script

Intern
    Onkologische Forschung

    Manfred Gessler: Mechanisms of pediatric kidney tumor formation

    Summary

    Molecular definition of pathways leading to malignant transformation of kidney precursor cells.
    Several culprit genes have been identified as drivers of oncogenesis in either Wilms tumors (e.g. WT1, CTNNB1, WTX, IGF2, SIX1/2, DROSHA, DGCR8, MYCN, TP53), or the less frequent clear cell sarcomas of the kidney (BCOR) and connatal mesoblastic nephroma (NTRK3, BRAF, EGFR). We utilize biochemical and cell biological approaches as well as mouse models to understand the molecular function of these mutant genes and to understand their contribution of oncogenesis: 2D and 3D primary tumor cell cultures can recapitulate many aspects of tumor growth in vivo and are amenable to genetic manipulation. Further mechanistic insight is gained by introduction of tumor-specific mutations into embryonic stem cells and transgenic mice, where their impact on kidney development and function can be followed.

    Recent Publications

    Williams RD, Chagtai T, Alcaide-German M, Apps J, Wegert J, Popov S, Vujanic G, van Tinteren H, van den Heuvel-Eibrink MM, Kool M, de Kraker J, Gisselsson D, Graf N, Gessler M, Pritchard-Jones K. Multiple mechanisms of MYCN dysregulation in Wilms tumour. Oncotarget. 2015; 6:7232-7243.

    The landscape of genomic alterations across childhood cancers. Gröbner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva VA, Johann PD, Balasubramanian GP, Segura-Wang M, Brabetz S, Bender S, Hutter B, Sturm D, Pfaff E, Hübschmann D, Zipprich G, Heinold M, Eils J, Lawerenz C, Erkek S, Lambo S, Waszak S, Blattmann C, Borkhardt A, Kuhlen M, Eggert A, Fulda S, Gessler M, Wegert J, Kappler R, Baumhoer D, Burdach S, Kirschner-Schwabe R, Kontny U, Kulozik AE, Lohmann D, Hettmer S, Eckert C, Bielack S, Nathrath M, Niemeyer C, Richter GH, Schulte J, Siebert R, Westermann F, Molenaar JJ, Vassal G, Witt H, Burkhardt B, Kratz CP, Witt O, van Tilburg CM, Kramm CM, Fleischhack G, Dirksen U, Rutkowski S, Frühwald M, von Hoff K, Wolf S, Klingebiel T, Koscielniak E, Landgraf P, Koster J, Resnick AC, Zhang J, Liu Y, Zhou X, Waanders AJ, Zwijnenburg DA, Raman P, Brors B, Weber UD, Northcott PA, Pajtler KW, Kool M, Piro RM, Korbel JO, Schlesner M, Eils R, Jones DTW, Lichter P, Chavez L, Zapatka M, Pfister SM. Nature. 2018; 555(7696):321-327.

    Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story. Kenny C, Bausenwein S, Lazaro A, Furtwängler R, Gooskens SL, van den Heuvel Eibrink M, Vokuhl C, Leuschner I, Graf N, Gessler M, O'Sullivan MJ. The Journal of pathology. 2016; 238(5):617-20.

    Characterization of primary Wilms tumor cultures as an in vitro model. Wegert J, Bausenwein S, Roth S, Graf N, Geissinger E, Gessler M. Genes, chromosomes & cancer. 2012; 51(1):92-104.

    Retinoic acid pathway activity in Wilms tumors and characterization of biological responses in vitro. Wegert J, Bausenwein S, Kneitz S, Roth S, Graf N, Geissinger E, Gessler M. Molecular cancer. 2011; 10:136.

    Kontakt

    Comprehensive Cancer Center Mainfranken
    Haus C16
    Josef-Schneider Str. 6
    97080 Würzburg

    Tel.: +49 931 201-35350
    Fax: +49 931 201-35359
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