Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are risk factors for colorectal cancer

Gastroenterology. 2013 Sep;145(3):544-7. doi: 10.1053/j.gastro.2013.06.001. Epub 2013 Jun 5.


The spindle assembly checkpoint controls proper chromosome segregation during mitosis and prevents aneuploidy-an important feature of cancer cells. We performed genome-wide and targeted copy number and mutation analyses of germline DNA from 208 patients with familial or early-onset (40 years of age or younger) colorectal cancer; we identified haploinsufficiency or heterozygous mutations in the spindle assembly checkpoint genes BUB1 and BUB3 in 2.9% of them. Besides colorectal cancer, these patients had variegated aneuploidies in multiple tissues and variable dysmorphic features. These results indicate that mutations in BUB1 and BUB3 cause mosaic variegated aneuploidy and increase the risk of colorectal cancer at a young age.

Keywords: CRC; Cancer Predisposition; MVA; Mosaic Variegated Aneuploidy; SAC; Spindle Assembly Checkpoint; colorectal cancer; mosaic variegated aneuploidy; spindle assembly checkpoint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Genome-Wide Association Study
  • Germ-Line Mutation*
  • Humans
  • Poly-ADP-Ribose Binding Proteins
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Risk Factors


  • BUB3 protein, human
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Poly-ADP-Ribose Binding Proteins
  • BUB1 protein, human
  • Protein-Serine-Threonine Kinases