Spindle Assembly checkpoint defects and colorectal cancer predisposition

Voer de, Richarda

In the coming issue of Gastroenterology, dr. Richarda de Voer from the group of dr. Roland Kuiper, together with several (inter)national collaborators, report that mutations in the spindle assembly checkpoint (SAC) genes BUB1and BUB3 lead to colorectal cancer predisposition. The spindle assembly checkpoint controls proper chromosome segregation during mitosis, thereby preventing aneuploidy, a hallmark of cancer. Mutations were identified in approximately 3% of patients with unexplained familial or early-onset colorectal cancer.

Biallelic mutations in another SAC gene, BUB1B, cause a severe syndrome characterized by mosaic variegated aneuploidy (MVA), microcephaly, intellectual disability and childhood cancers. Therefore, several patients with monoallelicBUB1andBUB3mutations were further characterized, and revealed mild congenital features, including facial dysmorphisms, as well as MVA in 23-38% of the lymphocytes and fibroblasts. These data provide a basis for improved diagnosis of individuals with an increased risk to develop colorectal cancer at a young age.

Germline Mutations in the Spindle Assembly Checkpoint Genes BUB1and BUB3 Are Risk Factors for Colorectal Cancer.  Gastroenterology 2013 Sep;145(3):544-547.


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