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

Richarda M de Voer, Ad Geurts van Kessel, Robbert D A Weren, Marjolijn J L Ligtenberg, Dominique Smeets, Lei Fu, Lilian Vreede, Eveline J Kamping, Eugène T P Verwiel, Marc-Manuel Hahn, Maayke Ariaans, Liesbeth Spruijt, Ton van Essen, Gunnar Houge, Hans K Schackert, Jian Q Sheng, Hanka Venselaar, Conny M A van Ravenswaaij-Arts, J Han J M van Krieken, Nicoline HoogerbruggeRoland P Kuiper

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)544-7
Number of pages4
JournalGastroenterology
Volume145
Issue number3
DOIs
Publication statusPublished - Sep 2013
Externally publishedYes

Keywords

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

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