Julia Schöpf, Sebastian Uhrig, Christoph E Heilig, Kwang-Seok Lee, Tatjana Walther, Alexander Carazzato, Anna Maria Dobberkau, Dieter Weichenhan, Christoph Plass, Mark Hartmann, Gaurav D Diwan, Zunamys I Carrero, Claudia R Ball, Tobias Hohl, Thomas Kindler, Patricia Rudolph-Hähnel, Dominic Helm, Martin Schneider, Anna Nilsson, Ingrid Øra, Roland Imle, Ana Banito, Robert B Russell, Barbara C Jones, Daniel B Lipka, Hanno Glimm, Daniel Hübschmann, Wolfgang Hartmann, Stefan Fröhling, Claudia Scholl
Linking clinical multi-omics with mechanistic studies may improve the understanding of rare cancers. We leverage two precision oncology programs to investigate rhabdomyosarcoma with FUS/EWSR1-TFCP2 fusions, an orphan malignancy without effective therapies. All tumors exhibit outlier ALK expression, partly accompanied by intragenic deletions and aberrant splicing resulting in ALK variants that are oncogenic and sensitive to ALK inhibitors. Additionally, recurrent CKDN2A/MTAP co-deletions provide a rationale for PRMT5-targeted therapies...
January 2, 2024: Nature Communications