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Molecular signatures of cutaneous squamous cell carcinoma in patients with Recessive Dystrophic Epidermolysis Bullosa

Project lead Dr Emmanuelle Bourrat
Organisation Centre de référence maladie rare MAGEC Hôpital Saint Louis, Paris, FRANCE
Partner organizations & collaborators Collaborators : Prof. Alain Hovnanian, Dr. Hélène Ragot, Dr. Matthias Titeux, Dr. Sonia Gaucher, Prof. Maxime Battistella INSERM UMR1163, Insitut IMAGINE; Departement de génétique, Hôpital Necker-Enfants Malades ; Service d’anatomo-pathologie, Hôpital Saint Louis, Paris, France; Other funders: Ligue contre le cancer
Project budget EUR 325,000.00
Start date / Duration 01. Sep 2018 / 60 months
Funder(s) / Co-Funder(s) DEBRA France
Research area Skin cancer & fibrosis

Project details

Short lay summary

Our research project investigates the molecular signatures of squamous cell carcinoma (SCC) and peri-tumoral dystrophic skin occurring in Recessive Dystrophic Epidermolysis Bullosa (RDEB) patients. The combination of different high-throughtput measurements by genomic next-generation sequencing (NGS), transcriptomic, and proteomic analyses of frozen tissues will allow to characterize altered mechanisms in SCC-RDEB and peri-tumoral dystrophic skin. A comparison of SCC-RDEB with UV-induced SCC from the general population by transcriptomic and proteomic analyses will enable the identification of specific molecular features. Finally, the analysis of SCC-RDEB from patients with an aggressive development has the potential to identify biological markers correlated with poor clinical outcomes (local recurrence or metastasis at 3 months).

Scientific summary

Recessive Dystrophic Epidermolysis Bullosa (RDEB) predisposes to the development of particularly aggressive cutaneous squamous cell carcinoma (SCC) at an early age, which represent the main cause of death before 40 years of age. Although recent data revealed that chronic skin damage is able to create a permissive tumor microenvironment in RDEB patients, a mechanistic understanding of SCC-RDEB development and of their invasive process is not completely elucidated.

Our project aims at identifying the molecular signatures in SCC and peri-tumoral dystrophic skin occurring in RDEB patients, using integrated and multi-omics approach including genomics, transcriptomics and proteomics. Somatic mutations will be analyzed by new-generation sequencing (NGS) using a 383 cancer-related gene panel developed in our laboratory. The identification of specific molecular signatures will provide complementary information on altered signalling pathways during cancer development. The identification of molecular signatures, biomarkers and/or recurrent altered signalling pathways in SCC-RDEB, correlated to the clinical outcomes (age of onset, aggressiveness, recurrence…) and compared to those of UV-induced SCC in non-RDEB patients, will pave the way for new strategies to develop innovative treatments.

Strategic relevance

This functional and multimodal approach collecting both genomic, transcriptomic and proteomic analyses will allow understanding specific mechanisms involved in cSCC-RDEB cells and their tumoral environment. Analysis of peri-tumoral dystrophic skin, yet unreported in the literature to our knowledge, may help to identify mechanisms by which the microenvironment in scarring skin favours SCC initiation in RDEB patients. Finally, the identification of molecular signatures, biomarkers and/or recurrent altered signalling pathways in SCC, and their correlation to clinical outcomes, will point to new therapeutic targets and strategies in addition to current treatment. 


squamous cell carcinoma
molecular signatures
next-generation sequencing
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