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Möhrmann, Lino; Werner, Maximilian; Oleś, Małgorzata; Mock, Andreas; Uhrig, Sebastian; Jahn, Arne; Kreutzfeldt, Simon; Fröhlich, Martina; Hutter, Barbara; Paramasivam, Nagarajan; Richter, Daniela; Beck, Katja; Winter, Ulrike; Pfütze, Katrin; Heilig, Christoph E.; Teleanu, Veronica; Lipka, Daniel B.; Zapatka, Marc; Hanf, Dorothea; List, Catrin; Allgäuer, Michael; Penzel, Roland; Rüter, Gina; Jelas, Ivan; Hamacher, Rainer; Falkenhorst, Johanna; Wagner, Sebastian; Brandts, Christian H.; Boerries, Melanie; Illert, Anna L.; Metzeler, Klaus H.; Westphalen, C. Benedikt; Desuki, Alexander; Kindler, Thomas; Folprecht, Gunnar; Weichert, Wilko; Brors, Benedikt; Stenzinger, Albrecht; Schröck, Evelin; Hübschmann, Daniel; Horak, Peter; Heining, Christoph; Fröhling, Stefan; Glimm, Hanno
Nature communications, 08/2022, Letnik: 13, Številka: 1Journal Article
Abstract The benefit of molecularly-informed therapies in cancer of unknown primary (CUP) is unclear. Here, we use comprehensive molecular characterization by whole genome/exome, transcriptome and methylome analysis in 70 CUP patients to reveal substantial mutational heterogeneity with TP53 , MUC16 , KRAS , LRP1B and CSMD3 being the most frequently mutated known cancer-related genes. The most common fusion partner is FGFR2 , the most common focal homozygous deletion affects CDKN2A . 56/70 (80%) patients receive genomics-based treatment recommendations which are applied in 20/56 (36%) cases. Transcriptome and methylome data provide evidence for the underlying entity in 62/70 (89%) cases. Germline analysis reveals five (likely) pathogenic mutations in five patients. Recommended off-label therapies translate into a mean PFS ratio of 3.6 with a median PFS1 of 2.9 months (17 patients) and a median PFS2 of 7.8 months (20 patients). Our data emphasize the clinical value of molecular analysis and underline the need for innovative, mechanism-based clinical trials.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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