Brief Report: Homozygous BUB1B Mutation and Susceptibility to Gastrointestinal Neoplasia.

被引：70

作者：

Frio, Thomas Rio ^{[1
,2
,3
,4
]}

Lavoie, Josee

Hamel, Nancy ^{[1
,2
,3
,4
]}

Geyer, Felipe C. ^{[8
]}

Kushner, Yael B.

Novak, David J. ^{[1
,2
,5
,6
]}

Wark, Landon ^{[9
]}

Capelli, Cristian ^{[10
]}

Reis-Filho, Jorge S. ^{[8
]}

Mai, Sabine ^{[9
]}

Pastinen, Tomi ^{[3
,4
,7
]}

Tischkowitz, Marc D. ^{[1
,2
,5
,6
]}

Marcus, Victoria A.

Foulkes, William D. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada

[2] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ, Canada

[3] McGill Univ, Ctr Hlth, Dept Med Genet, Montreal, PQ, Canada

[4] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada

[5] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Med Genet, Montreal, PQ H3T 1E2, Canada

[6] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada

[7] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3T 1E2, Canada

[8] Breakthrough Breast Canc Res Ctr, Inst Canc Res, London, England

[9] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada

[10] Univ Oxford, Dept Zool, Oxford OX1 3PS, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 363卷 / 27期

关键词：

MOSAIC VARIEGATED ANEUPLOIDY; HUMAN MITOTIC MUTANT; COLORECTAL CANCERS; CHROMATID SEPARATION; SPINDLE CHECKPOINT; BUBR1; PROTEIN; INSTABILITY; INHIBITION; EXPRESSION;

D O I：

10.1056/NEJMoa1006565

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

A patient received a diagnosis of adenocarcinoma of the ampulla of Vater at 34 years of age. Two decades later, adenomatous polyps were found, followed by multiple primary invasive adenocarcinomas of both the colon and the stomach. Premature chromatid separation and mosaic variegated aneuploidy, combined with structural chromosomal abnormalities, were detected in his cells. We identified a germline homozygous intronic mutation, c.2386-11A(rightarrow)G, in the spindle-assembly checkpoint gene BUB1B, which creates a de novo splice site that is favored over the authentic (i.e., preferentially used) site. Our findings expand the phenotype associated with BUB1B mutations and the mosaic variegated aneuploidy syndrome to include common adult-onset cancers and provide evidence for the interdependency of the APC protein (encoded by the adenomatous polyposis coli gene) and the BUBR1 protein (encoded by BUB1B) in humans. (Funded by the Turner Family Cancer Research Fund and others.).

引用

页码：2628 / 2637

页数：10

共 27 条

[1]

Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers [J].