Evolutionary dynamics of Leucoplakias in Fanconi anaemia patients

• Applicant: Dr. Eunike Velleuer
• Subject Area: Anatomy and Physiology ; Hematology, Oncology ; Human Genetics ; Medical Informatics and Medical Bioinformatics
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530200248

Fanconi Anemia (FA) is a rare genetic disorder, in which constitutive DNA repair defects can lead to aplasia or cancer, and a drastic reduction in life expectancy, generally not exceeding 20-30 years. FA patients often present with leucoplakias, pre-malign lesions of the oral cavity associated with a higher risk of oral squamous cell carcinoma (OSCC). Therapies can involve hematopoietic stem cell transplantation (HSCT), which improves overall survival but also increases the risk of developing OSCC. We however still lack quantitative information on how FA influences somatic evolution in the oral cavity. Here we aim to uncover how FA and its treatment affect the evolutionary dynamics of oral mucosa cells and leucoplakias. By comparing DNA sequencing data from oral cytobrush samples between healthy subjects and FA patients, we will quantify the impact of FA on the number of mutations, the genes under positive selection, and the mutational processes at work and in the normal-looking oral mucosa. To understand the molecular bases behind leucoplakia prominence in FA patients, we will investigate their genetic and environmental profiles in this specific background. Finally, we will compare transplanted and non-transplanted FA patients, to better characterize how HSCT influences pre-malignant lesion formation in these patients. The consortium includes biologists, medical doctors and bioinformaticians, with strong expertise on Fanconi anemia, pre-malignant lesions, evolutionary dynamics and the immune micro-environment. Necessary logistics, sample collections and adequate methodological solutions have already been implemented. This project will provide a better understanding of how FA impacts evolutionary dynamics in the oral cavity, paving the way for better prevention and intervention strategies.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Dr. Pierre Martinez