Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.
Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.
复制标题
DOI：
--
复制
发表时间：
2002-07
期刊：
影响因子：
11.2
通讯作者：
Y. Mori;F. Sato;F. Selaru;Andreea Olaru;K. Perry;M. Kimos;G. Tamura;N. Matsubara;Suna Wang;Yan Xu;Jing Yin;T. Zou;B. Leggett;Joanne P Young;T. Nukiwa;O. Stine;J. Abraham;D. Shibata;S. Meltzer
中科院分区：
文献类型：
--
作者：
Y. Mori;F. Sato;F. Selaru;Andreea Olaru;K. Perry;M. Kimos;G. Tamura;N. Matsubara;Suna Wang;Yan Xu;Jing Yin;T. Zou;B. Leggett;Joanne P Young;T. Nukiwa;O. Stine;J. Abraham;D. Shibata;S. Meltzer
编码区内的微卫星不稳定性（MSI）导致移码突变（FSM）。这种类型的突变可能会破坏常见MSI（MSI-H癌症）癌症中的肿瘤抑制基因。为了以公正和全面的方式鉴定胃癌发生中的新FSM，我们在18例MSI-H胃癌中筛选了154个编码区重复位点的这种类型的突变。我们还比较了MSI-H胃癌与结直肠癌的FSM率和光谱。13个新的基因座在>20%的胃肿瘤中显示FSM。突变频率最高的新位点包括激活素2型受体基因（44.4%）、DKFZp 564 K112（果蝇肿瘤抑制基因多性别梳的同源物; 41.2%）和内质网伴侣蛋白基因SEC 63（37.5%）。MSI-H胃癌和结直肠癌中高突变频率基因的突变谱也有显著差异。
Microsatellite instability (MSI) within coding regions causes frameshift mutations (FSMs). This type of mutation may inactivate tumor suppressor genes in cancers with frequent MSI (MSI-H cancers). To identify novel FSMs in gastric carcinogenesis in an unbiased and comprehensive manner, we screened for this type of mutation at 154 coding region repeat loci in 18 MSI-H gastric cancers. We also compared FSM rates and spectra in MSI-H gastric versus colorectal cancers. Thirteen novel loci showed FSMs in >20% of gastric tumors. Novel loci with the highest mutation frequencies included the activin type 2 receptor gene (44.4%), DKFZp564K112 (a homologue of the Drosophila tumor suppressor gene multi-sex-combs; 41.2%), and an endoplasmic reticulum chaperone protein gene SEC63 (37.5%). The mutational spectra for genes with high mutation frequencies were also significantly different between MSI-H gastric and colorectal cancers.