Functional analysis of the genomic abnormalities of non UV-induced skin squamous cell carcinomas
Grantee: Dany Nassar, MD, PhD, Associate Professor, Department of Dermatology, Université Paris
Amount: DKK 952,095
Grant category: Research grants in open competition
Squamous cell carcinoma (SCC) of the skin is the second most frequent skin cancer. Generally, SCC occurs on sun-exposed areas of fair skinned in elderly individuals.
However, skin carcinogenesis is also observed in non-UV induced settings, particularly in chronic wounds and scars like chronic leg ulcers, inherited blistering diseases and deep burn scars. These wound-associated SCCs are highly invasive and prone to metastasis, making them a life threatening complication.
The mechanisms of chronic wound carcinogenesis are unknown. The absence of UV exposure and different clinical behaviour suggest different mechanisms of carcinogenesis, including different initiating driver genomic abnormalities.
The team behind this study aims to uncover genomic alterations through Whole Exome Sequencing on a cohort of 35 wound/scar-associated SCCs with matching germline DNA. They will compare achieved data to data on UV-induced SCCs and to murine models of skin SCCs.
Furthermore, they will perform micro-dissection of successive stages of carcinogenesis in a cohort of specimen and subject these to targeted genotyping. This will allow for determination of the successive genetic alterations that drive the multistep carcinogenesis in the absence of carcinogenic UV exposure.
The team expects to find a distinct and hopefully new mutational signature in skin carcinogenesis, to identify new oncogenes and tumour suppressor genes and to model the multistep genomic evolution of wound/scarring associated skin SCC.
Basis for the project lies in a multicentre collaboration gathering six University Hospitals in two countries, including Paris-based Hôpital Cochin and Hôpital Tenon as well as American University of Beirut Medical Centre in Lebanon.