Mapping how protective genes fail and allow cancer to grow

Benjamin Lehner

Fundació Centre de Regulació Genòmica (CRG), Spain

Cancer often develops when genes that prevent uncontrolled cell division stop working properly. While researchers know many of these protective genes, they still cannot determine which mutations are harmful or how they disrupt gene function. This project aims to address this knowledge gap by creating detailed maps of the changes that damage cancer-protective genes and allow abnormal growth.

The team brings together expertise in cancer genomics, large-scale screening, method development and data analysis to build a reference resource for interpreting cancer genomes. The team will use large-scale experimental approaches to test thousands of possible genetic changes and identify those that interfere with gene activity. They will also investigate genes that regulate the activity of other genes, to understand how mutations alter wider cellular programmes.

The results are expected to throw light on how individual mutations contribute to cancer development, patient outcomes and responses to treatment. By revealing the mechanisms behind each mutation, the project may pave the way for precision cancer therapies targeting the specific mechanism that drives each tumour.

• Antoni Beltran, Agencia Estatal Consejo Superior de Investigaciones Científicas, M.P., Spain

• Solip Park, Fundación del Sector Público Estatal Centro Nacional de Investigaciones Oncológicas Carlos III, Spain

Massive scale experimental quantification of variant effects in human tumor suppressor genes

€999,425.77