Prognosis estimation in malignant melanoma based on changes in tumor genome

• Applicant: Katharina Ginter
• Subject Area: Dermatology ; Hematology, Oncology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 535704065

Malignant melanoma is a common type of tumor in Germany, with approximately 19 cases per 100,000 inhabitants per year. In contrast to other tumor entities, the incidence is comparatively high at a young age. Moreover, with inconspicuous skin aspect and lack of symptoms, it is often discovered late and forms metastases early. Despite the introduction of new immunotherapies, mortality from metastatic melanoma remains high. During my research stay, I would like to contribute to the earlier and more targeted use of new immunotherapies with the help of a prognosis assessment algorithm. This is intended to lead to a more effective therapy and a higher probability of survival in malignant melanoma. The current medical guideline recommends considering drug immunotherapy only from stage III (lymph node metastases). However, at this stage, the genetic diversity of the tumor cells is already advanced, which increases the likelihood of resistant subclones. Adjuvant drug therapy at earlier stages could increase the chances of cure. However, this carries the risk of unnecessarily treating and thus harming patients with a low risk of progression. Therefore, the aim of our research will be to investigate the association between tumor progression and various parameters such as genetic alterations, tumor stroma status or tumor-directed immune responses. During my research stay at the Helen Diller Family Comprehensive Cancer Center, San Francisco, USA, two risk-matched cohorts of 200 patients each will be selected from an existing patient database from 2002-2015. In a next step, mutation and copy number of melanoma relevant genes as well as genome-wide changes in DNA copy number and heterozygosity will be determined. This information will be statistically evaluated to identify genetic alterations associated with an increased risk of tumor progression. The model will then be tested in another independent cohort of 300 patients and compared with traditional prognostic markers such as tumor thickness, ulceration, gender, anatomical location or sentinel lymph node status. The aim of the research is to develop and validate a prototype for a clinical test to assess the risk of progression of malignant melanoma. Future criteria for earlier adjuvant drug therapy in malignant melanoma can be based on this.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Boris Christoph Bastian