#IDIBELLfellows: Manuel Torralba

Modelling the Origin of Glioblastoma in Mismatch Repair Deficiency Syndromes
 Manuel Torralba Carnerero – Hereditary cancer group
The DNA mismatch repair (MMR) system is responsible for correcting DNA mismatches introduced by DNA polymerases during DNA replication. The MMR system is comprised of four main genes: MLH1, MSH2, MSH6 and PMS2. Carrying a loss-of-function mutation in any of these four genes in the germline predisposes to Lynch syndrome (LS). The biallelic counterpart is the Constitutional Mismatch Repair Deficiency (CMMRD), a rare childhood-onset cancer predisposition syndrome. Together with LS, constitute the DNA mismatch repair deficiency (MMR-D) syndromes. Glioblastoma is the most frequently diagnosed tumour in CMMRD. However, the mechanisms underlying this malignant transformation are still poorly understood.
In this project, we developed an MMR-deficient iPSC-derived neural progenitor cell (NPC) model that might be relevant for the characterization of early molecular events contributing to glioblastoma development in MMR-D syndromes.