Cancer Genomics & Proteomics

Stephan Bernhardt, Simone Borgoni, Emre Sofyali, Mireia Berdiel, Cindy Körner, Leonie Wahjudi, Khalid Abnaof

Genomic and epigenetic alterations in cancer genomes are initial drivers of disease. We are out to characterize such driver events particularly in less-studied tumor entities. Furthermore, genomic events impinge on the tumor proteome. We evaluate whether protein abundance and activation qualify as diagnostic, prognostic or predictive markers.

Cancer is commonly regarded as ‘a disease of the genes’. Alterations in abundance (copy number variation – CNV) or sequence (single nucleotide variation – SNV, insertions, deletions) and larger genomic rearrangements indeed affect individual or many genes thus contributing to disease onset and progression. Along these lines we have unraveled causal variants in a range of tumor entities [Agaimy et al. 2014, Barthelmess et al. 2014, Haller et al. 2015, Haller et al. 2016, Agaimy et al. 2017]. Ongoing projects focus on other sarcoma entities as well as on B-cell lymphoma and metastasized breast cancer (DKFZ-HIPO).

Changes in the epigenetic state of chromatin (DNA, histones) add to the complexity of aberrations. We have identified micro-RNAs and epigenetic signatures that are of diagnostic or prognostic value in different entities [Haller et al. 2010, Haller et al. 2015, Bure et al. 2017]. In ongoing projects we determine epigenetic changes related to therapy resistance in breast cancer (EU EpiPredict).

Whilst genomic and transcriptomic data are easily accessible and starting to be used in clinical practice, it is proteins and protein activities that are mostly targeted in therapies. Using reverse phase protein array technology we address clinically druggable pathways. Key phosphorylated and non-phosphorylated proteins are quantified in clinical samples to determine a potential benefit towards therapy recommendation of having proteomic information on top of genetic and genomic data.

Collaborations

Sarcoma: Florian Haller, Abbas Agaimy, Arndt Hartmann (Erlangen)

Breast cancer: Christel Herold-Mende, Andreas Schneeweiss, Clarissa Gerhäuser, Naveed Ishaque (Heidelberg), Martina Vetter, Eva Kantelhardt (Halle/Saale), Jens Timmer (Freiburg), Tim Beissbarth (Göttingen), Max Hasmann (Penzberg), Niels de Jonge (Saarbrücken)

Primary CNS Lymphoma: Christel Herold-Mende, Naveed Ishaque (Heidelberg), Frank Heppner (Berlin)

NCT-MASTER: Stefan Fröhling, Hanno Glimm (Heidelberg)

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