TY  - JOUR
A1  - Gröbner, Susanne N.
A1  - Worst, Barbara C.
A1  - Weischenfeldt, Joachim
A1  - Buchhalter, Ivo
A1  - Kleinheinz, Kortine
A1  - Rudneva, Vasilisa A.
A1  - Johann, Pascal D.
A1  - Balasubramanian, Gnana Prakash
A1  - Segura-Wang, Maia
A1  - Brabetz, Sebastian
A1  - Bender, Sebastian
A1  - Hutter, Barbara
A1  - Sturm, Dominik
A1  - Pfaff, Elke
A1  - Hübschmann, Daniel
A1  - Zipprich, Gideon
A1  - Heinold, Michael
A1  - Eils, Jürgen
A1  - Lawerenz, Christian
A1  - Erkek, Serap
A1  - Lambo, Sander
A1  - Waszak, Sebastian
A1  - Blattmann, Claudia
A1  - Borkhardt, Arndt
A1  - Kuhlen, Michaela
A1  - Eggert, Angelika
A1  - Fulda, Simone
A1  - Gessler, Manfred
A1  - Wegert, Jenny
A1  - Kappler, Roland
A1  - Baumhoer, Daniel
A1  - Stefan, Burdach
A1  - Kirschner-Schwabe, Renate
A1  - Kontny, Udo
A1  - Kulozik, Andreas E.
A1  - Lohmann, Dietmar
A1  - Hettmer, Simone
A1  - Eckert, Cornelia
A1  - Bielack, Stefan
A1  - Nathrath, Michaela
A1  - Niemeyer, Charlotte
A1  - Richter, Günther H.
A1  - Schulte, Johannes
A1  - Siebert, Reiner
A1  - Westermann, Frank
A1  - Molenaar, Jan J.
A1  - Vassal, Gilles
A1  - Witt, Hendrik
A1  - Burkhardt, Birgit
A1  - Kratz, Christian P.
A1  - Witt, Olaf
A1  - van Tilburg, Cornelis M.
A1  - Kramm, Christof M.
A1  - Fleischhack, Gudrun
A1  - Dirksen, Uta
A1  - Rutkowski, Stefan
A1  - Frühwald, Michael
A1  - Hoff, Katja von
A1  - Wolf, Stephan
A1  - Klingebeil, Thomas
A1  - Koscielniak, Ewa
A1  - Landgraf, Pablo
A1  - Koster, Jan
A1  - Resnick, Adam C.
A1  - Zhang, Jinghui
A1  - Liu, Yanling
A1  - Zhou, Xin
A1  - Waanders, Angela J.
A1  - Zwijnenburg, Danny A.
A1  - Raman, Pichai
A1  - Brors, Benedikt
A1  - Weber, Ursula D.
A1  - Northcott, Paul A.
A1  - Pajtler, Kristian W.
A1  - Kool, Marcel
A1  - Piro, Rosario M.
A1  - Korbel, Jan O.
A1  - Schlesner, Matthias
A1  - Eils, Roland
A1  - Jones, David T. W.
A1  - Lichter, Peter
A1  - Chavez, Lukas
A1  - Zapatka, Marc
A1  - Pfister, Stefan M.
T1  - The landscape of genomic alterations across childhood cancers
JF  - Nature
N2  - Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
KW  - cancer genomics
KW  - oncogenesis
KW  - paediatric cancer
KW  - predictive markers
KW  - translational research
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579
VL  - 555
ER  - 
TY  - JOUR
A1  - Wallaschek, Nina
A1  - Reuter, Saskia
A1  - Silkenat, Sabrina
A1  - Wolf, Katharina
A1  - Niklas, Carolin
A1  - Özge, Kayisoglu
A1  - Aguilar, Carmen
A1  - Wiegering, Armin
A1  - Germer, Christoph-Thomas
A1  - Kircher, Stefan
A1  - Rosenwald, Andreas
A1  - Shannon-Lowe, Claire
A1  - Bartfeld, Sina
T1  - Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids
JF  - PLoS Pathogens
N2  - Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.
KW  - Organoids
KW  - ephitelial cells
KW  - gastrointestinal infections
KW  - cancers and neoplasms
KW  - Epstein-Barr virus
KW  - flow cytometry
KW  - epithelium
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259206
VL  - 17
IS  - 2
ER  - 
TY  - JOUR
A1  - Pattschull, Grit
A1  - Walz, Susanne
A1  - Gründl, Marco
A1  - Schwab, Melissa
A1  - Rühl, Eva
A1  - Baluapuri, Apoorva
A1  - Cindric-Vranesic, Anita
A1  - Kneitz, Susanne
A1  - Wolf, Elmar
A1  - Ade, Carsten P.
A1  - Rosenwald, Andreas
A1  - von Eyss, Björn
A1  - Gaubatz, Stefan
T1  - The Myb-MuvB complex is required for YAP-dependent transcription of mitotic genes
JF  - Cell Reports
N2  - YAP and TAZ, downstream effectors of the Hippo pathway, are important regulators of proliferation. Here, we show that the ability of YAP to activate mitotic gene expression is dependent on the Myb-MuvB (MMB) complex, a master regulator of genes expressed in the G2/M phase of the cell cycle. By carrying out genome-wide expression and binding analyses, we found that YAP promotes binding of the MMB subunit B-MYB to the promoters of mitotic target genes. YAP binds to B-MYB and stimulates B-MYB chromatin association through distal enhancer elements that interact with MMB-regulated promoters through chromatin looping. The cooperation between YAP and B-MYB is critical for YAP-mediated entry into mitosis. Furthermore, the expression of genes coactivated by YAP and B-MYB is associated with poor survival of cancer patients. Our findings provide a molecular mechanism by which YAP and MMB regulate mitotic gene expression and suggest a link between two cancer-relevant signaling pathways.
KW  - YAP
KW  - B-MYB
KW  - Myb-MuvB
KW  - mitotic genes
KW  - enhancer
KW  - transcription
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202039
VL  - 27
IS  - 12
ER  -