NMSCP-Gustav Roussey

Program Description

This is the first large-scale genomic study of Non-Melanoma Skin Cancer with the focus on Basal Cell Carcinoma and Squamous Cell Carcinoma of skin. In frames of this study WGS of 100 tumors and WES of 200 tumors are produced. In parallel a subset of tumors is subjected to RNAseq and methylation profiling. As a control, RNAseq and methylation is performed for a sample of adjacent skin, considered as a tissue of origin for keratinocyte cancers. The study pursues the following scopes: (i) identification of the driver genes and driver mutations; (ii) investigation of the role of mutations in gene promoter regions on gene expression; (iii) association of molecular features with tumor histology; (iv) deconvolution of mutational signatures from mutational profiles in comparison with skin melanoma.

Program Goals and Expected Outcomes

While a lot of attention was dedicated to genomics of Melanoma, Non-Melanoma Skin Cancer and particularly Basal Cell Carcinoma of skin, remains largely unstudied. Currently BCCs are treated with excision or with Hedgehog blockers, such as vismodegib. Despite frequent impressive initial response to vismodegib, up to 30% of BCC relapse on treatment or after its discontinuation, highlighting unmet need for improvement of treatment strategies. Our recent study revealed that BCC are hypermutable tumors, and suggested the interaction of several cancer pathways during BCC progression. Current study aims to provide a detailed picture of driver mutational landscape in BCC unraveling associations between mutations and Clinico-Pathological characteristics of patients.

What gaps in existing knowledge will be addressed by the study?

This is the first genomic study of Non-Melanoma Skin Cancers (NMSC) including BCC and SCC. The driver genes and cancer pathways network in those cancers are understudied.  Providing histological similarities between advanced BCC and SCC, it is expected that genetic similarities will be also observed. Uncertainties in the cell of origin of BCC and SCC could be addressed with mutational profiling; mutagenesis reflects the chromatin status in the genomic loci, and may point to the tissues of origin. Our initial analyses revealed differences in the mutational signatures between NMSC and melanoma, and the etiology of such differences is not understood.

Program Team

Sergey Nikolaev

Lead Investigator

Funding Organisations

Further Information

PROJECT WEBSITE