Germline Mutations in the Spindle Assembly Checkpoint Genes BUB1 and BUB3 Are Risk Factors for Colorectal Cancer

被引：79

作者：

de Voer, Richarda M. ^{[1
]}

van Kessel, Ad Geurts ^{[1
]}

Weren, Robbert D. A. ^{[1
]}

Ligtenberg, Marjolijn J. L. ^{[1
,2
]}

Smeets, Dominique ^{[1
]}

Fu, Lei ^{[3
,4
]}

Vreede, Lilian ^{[1
]}

Kamping, Eveline J. ^{[1
]}

Verwiel, Eugene T. P. ^{[1
]}

Hahn, Marc-Manuel ^{[1
]}

Ariaans, Maayke ^{[1
]}

Spruijt, Liesbeth ^{[1
]}

van Essen, Ton ^{[5
]}

Houge, Gunnar ^{[6
]}

Schackert, Hans K. ^{[7
]}

Sheng, Jian Q. ^{[3
]}

Venselaar, Hanka ^{[8
]}

van Ravenswaaij-Arts, Conny M. A. ^{[5
]}

van Krieken, J. Han J. M. ^{[2
]}

Hoogerbrugge, Nicoline ^{[1
]}

Kuiper, Roland P. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands

[3] Gen Hosp Beijing Mil Region, Dept Gastroenterol, Beijing 100700, Peoples R China

[4] Third Mil Med Univ, Chongqing, Peoples R China

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[6] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

[7] Tech Univ Dresden, Dept Surg Res, Univ Klinikum Carl Gustav Carus, D-01062 Dresden, Germany

[8] Nijmegen Ctr Mol Life Sci, Ctr Mol & Biomol Informat, Nijmegen, Netherlands

来源：

GASTROENTEROLOGY | 2013年 / 145卷 / 03期

关键词：

Cancer Predisposition; Spindle Assembly Checkpoint; Mosaic Variegated Aneuploidy;

D O I：

10.1053/j.gastro.2013.06.001

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：544 / 547

页数：4

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