Deciphering genomic aberrations in rare skin cancers to find mechanism-based treatment strategies
01.03.2017 – 28.02.2021
Tumors are driven by (epi-)genomic aberrations that can, in principle, be pharmaceutically targeted. Such mechanism-based therapies had already remarkable impact on the clinical care of patients with common cancers. Yet, the genomic aberrations in rare cancers and their therapeutic potential are largely unknown.
In this project, we will determine the genomic landscape of various histologically well-defined subgroups of rare skin cancer, in particular of Merkel cell carcinoma and of various specific subtypes of adnexal carcinoma and melanocytic tumors. We will assess the biological relevance of the recurrently identified genomic aberrations in existing and novel patient-derived models to get insights into the pathways driving tumorigenesis and metastasis. Lastly, we will evaluate the efficacy of drugs targeting these pathways, and study potential drug resistance mechanisms that may limit their efficacy. Using this strategy, we are
confident to refine the classification system of specific subtypes of skin cancer, and to pave the way for mechanism-based treatment strategies to improve the overall survival of patients. The proposed project builds on a unique and well-characterized set of patient samples (provided by an international network of pathologists and clinicians) and on industry partnerships providing sequencing support, and combines state-of-the-art genomic techniques with disease- and therapy-oriented functional assays.
Publications
- Haas L., Wiesner T., Obenauf A. C. (2018) A new era of proactive melanoma therapy: hit hard, hit early, British Journal of Dermatology 178/4: 817-820
- Griewank Klaus G, Wiesner Thomas, Murali Rajmohan, Pischler Carina, Müller Hansgeorg, Koelsche Christian, Möller Inga, Franklin Cindy, Cosgarea Ioana, Sucker Antje, Schadendorf Dirk, Schaller Jörg, Horn Susanne, Brenn Thomas, Mentzel Thomas (2017) Atypical fibroxanthoma and pleomorphic dermal sarcoma harbor frequent NOTCH1/2 and FAT1 mutations and similar DNA copy number alteration profiles, Modern Pathology 31/3: 418-428
- Busam Klaus J, Pulitzer Melissa P, Coit Daniel C, Arcila Maria, Leng Danielle, Jungbluth Achim A, Wiesner Thomas (2017) Reduced H3K27me3 expression in Merkel cell polyoma virus-positive tumors, Modern Pathology 30/6: 877-883