Hereditary diffuse gastric cancer due to a previously undescribed CDH1 splice site mutation

被引:13
作者
Matsukuma, Karen E. [1 ]
Mullins, Franklin M. [1 ]
Dietz, Lisa [1 ]
Zehnder, James L. [1 ]
Ford, James M. [2 ,3 ]
Chun, Nicolette M. [2 ]
Schrijver, Iris [1 ,3 ]
机构
[1] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Med Oncol, Sch Med, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA
关键词
HDGC; CDH1; Gastric cancer; Mutation; Splicing; GERMLINE MUTATIONS; FAMILIES;
D O I
10.1016/j.humpath.2010.01.022
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Our patient was a 52-year-old man who was diagnosed with signet ring cell gastric adenocarcinoma. An extensive family history of gastric cancer raised suspicion for hereditary diffuse gastric cancer. Sequencing of the patient's CDH1 gene revealed a novel point mutation in a strictly conserved splice site within intron 6, c.833-2 A > G. This mutation was predicted to result in loss of function due to defective RNA splicing. To characterize the pathogenic mechanism of this mutation, we amplified the patient's CDH1 gene products by reverse transcriptase polymerase chain reaction. Primers flanking the region of the mutation detected 3 distinct transcripts. In addition to the wild-type product, a larger product consistent with activation of a cryptic splice site within intron 6 and a smaller product shown to result from exon 7 skipping were detected. In summary, we have identified a novel CDH1 mutation in a large hereditary diffuse gastric cancer kindred and identified its pathogenic mechanism. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:1200 / 1203
页数:4
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