Approved research

Defining the role of CRYBG1 germline alterations on tumor incidence and progression

Lay summary

Cancer's most feared feature is its ability to invade into benign tissues and spread to distant sites. Every cell has a structural scaffold, a skeleton termed the cytoskeleton. It consists of a complex interlinked network of proteins that supports the cell and helps to maintain its shape. To invade other tissues, cancer cells need to alter their cytoskeletal properties to become malleable enough to change their shape and to move through tissues. We have recently unmasked an important protein, named CRYBG1 that regulates the cytoskeleton in benign cells and is dysfunctional in cancer. When CRYBG1 is present, the cells' scaffolding keeps it rigid and correct shape. When CRYBG1 function is lost, cells can remodel their cytoskeleton more frequently change their shape and become capable of invading and migrating to distant locations. Importantly, we have found that the CRYBG1 gene is frequently disrupted in the germline (the DNA sequence shared by all cells in the body) in patients who develop very aggressive forms of metastatic prostate cancer. We therefore hypothesize that genetic alterations in CRYBG1 give cancer cells an early advantage to change shape, migrate, invade and to spread to different tissues. In this study we aim to examine if these germline genomic alterations in CRYBG1 are present in patients with cancer and if the presence of CRYBG1 mutations is associated with aggressive disease. This information will provide the basis for a novel genetic test for aggressive forms of cancer. Ultimately, we hope that this research will improve the care and survival of patients suffering from cancer and their families.