Absence of aneuploidy and gastrointestinal tumours in a man with a chromosomal 2q13 deletion and BUB1 monoallelic deficiency.
Absence of aneuploidy and gastrointestinal tumours in a man with a chromosomal 2q13 deletion and BUB1 monoallelic deficiency.
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DOI：
10.1136/bcr-2013-008684
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发表时间：
2013-02-25
期刊：
影响因子：
0.9
通讯作者：
Narayan, Deepak
中科院分区：
文献类型：
--
作者：
Hoang, Don;Sue, Gloria R;Narayan, Deepak
染色体不稳定性是结直肠癌发展的潜在关键步骤。BUB1基因是一种高度保守的蛋白，在细胞分裂过程中纺锤体组装检查点起关键作用。BUB1突变以显性负性方式发挥作用，并与着丝点附着功能失调、染色单体过早分离、全染色体加速错误分离和非整倍体有关。在结直肠癌患者中观察到BUB1突变。我们报告了一例因2q13染色体缺失1.7 Mb而导致的BUB1单倍性不全，患者为54岁男性，既往无癌史。在手部组织和外周血中均观察到这些突变等位基因。细胞遗传学分析未发现非整倍体。这些发现强调了BUB1单倍不全直接刺激肿瘤发生的不足，并提示其他因素可能对这一过程更为关键。
Chromosomal instability is a potentially critical step in the development of colorectal cancer. The budding uninhibited by benzimidazole 1 (BUB1) gene is a highly conserved protein that plays a critical role at the spindle assembly checkpoint during cell division. BUB1 mutations function in a dominant-negative fashion and have been implicated in causing dysfunctional kinetochore attachments, premature chromatid separation, accelerated mis-segregation of whole chromosomes and aneuploidy. BUB1 mutations have been observed in patients with colorectal cancers. We report a remarkable case of BUB1 haploinsufficiency owing to a 1.7 Mb deletion of chromosome 2q13 in a 54-year-old man with no prior history of carcinoma. These mutant alleles were observed in both tissue from the hand and peripheral blood. Aneuploidy was not observed on cytogenetic analysis. These findings highlight the insufficiency of BUB1 haploinsufficiency to directly stimulate tumourigenesis, and suggest that other factors may be more critical to this process.