IP: Dres. Gema Moreno-Bueno y Pablo García Sanz

Resumen del proyecto: Defects in cell cycle control are one of the hallmarks of tumor cells. In the vast majority of human cancers, the regulation of this process is altered. Among the various factors that take part the anaphase promoting complex (APC/C) ¡s of great importance. The APC/C is a multi-protein complex with ubiquitin ligase activity. On one hand, APC/C is necessary for the transition from metaphase to anaphase during mitosis, and on the other it takes part in maintaining the cell in Gl phase of the cell cycle. Cdc27 protein is one of the components of this complex, in which it acts as a scaffold mediating the interaction of other proteins. This function is allowed by specialized protein-protein interaction domains called TPR. In our research group, we have performed exorne sequencing experiments with endometrial carcinoma and carcinosarcoma samples. These analyses have allowed us to detect a high number of variants in the CDC27 gene. In the case of the carcinosarcomas, the variants are found on the región corresponding to certain TPR domains, while in the carcinomas we detected, among others, a missense variant. In both cases, the variants were also found in matched samples of normal tissue, suggesting that germline alterations in this gene could be related to endometrial tumorigenesis, being potentials markers for disease susceptibility. To test this hypothesis, we have a collection of endometrial tissue samples, both tumoral and normal tissue, and also endometrial benign hyperplasias. In order to complete the study, we need to analyse DNA samples from healthy individuáis.

Entidad financiadora: Asociación Española Contra el Cáncer