Short summary

Rare skin cancers, such as merkel cell carcinoma and sebaceous carcinoma, remain incurable and unexplained. The purpose of this study is to identify the protein profile of rare skin cancers and use the analyses to investigate disease pathways and mechanisms. The results will provide a broader understanding of the disease mechanisms and potentially reveal new targets for drug development, as well as nominate molecular biomarkers of rare skin cancers for diagnostic tool development.

Rationale

The range of skin diseases is staggering as one in four people on the planet suffers from a skin disease at any given time. Although most skin diseases are mild and may clear away without treatment, some, including rare skin cancers, are life-threatening and extreme. Furthermore, etiology and molecular mechanisms that drive many of these cancers remain unknown, making their diagnosis, treatment, and monitoring difficult, and patient prognosis uncertain. Therefore, rare skin cancers represent a significant unmet medical need with poor prognosis for millions of patients and given that rare skin cancers diagnosis have been on the rise, they are on course of becoming a significant burden on health care systems. This highlights the urgent need for better understanding and more complete characterization of rare skin cancers. Over the last five years, we developed powerful mass spectrometry (MS)-based proteomics strategies for characterization of both healthy and diseased skin, revealing previously unknow details of the skin's proteome. These efforts culminated in the first Human Skin Atlas that holds information on almost 11,000 proteins and their distribution across all the layers of the healthy skin. Here, we propose to conduct a systematic proteomic characterization of rare skin cancers using archival tissue from the National Pathology Register system (Patobank) at the department of Pathology, Odense and Næstved University Hospital. The project will provide a better understanding of pathological and physiological changes in these skin cancers. We expect that these insights will lead to identification of potential targets for development of more effective treatment strategies. Furthermore, we will pursue identification and validation of biomarkers that could be used for the diagnosis of rare skin cancers. Taken together, the MS-based proteomic study of rare skin cancers will represent a major advancement for the field, and open broad ranging opportunities to address this growing, yet unmet medical need. Overall purpose of the research proposal: The specific ability of MS-based proteomics to analyze archived human FFPE tumor tissue samples offer numerous possibilities to advance translational dermatological research, including identifying mechanisms responsible for disease pathology. This research proposal is based on four project aims: 1) To create a cohort of rare skin cancers from archival samples of FFPE tissue (Patobank) and characterize the proteome of these rare skin cancer samples using MS-based proteomics. 2) To investigate the prevalence of viral peptides in the skin tumors. 3) To identify and characterize new potential medical targets in rare skin cancers. 4) To investigate the potential of MS-based diagnostics of rare skin cancers.

Description of the cohort

Around 20 samples from each tumortype is included.

Data and biological material

Formalin fixed parafin embedded tissue identified using Patopank.

Collaborating researchers and departments

Department of Dermatology, Gentofte hospital

• Beatrice Dyring Andersen
• Marianne Løvendorf
• Ying Zhang