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Frequent mutations of human Mad2, but not Bub1, in gastric cancers cause defective mitotic spindle checkpoint

Authors
 Han-Soo Kim  ;  Kyung Hwa Park  ;  Sun A Kim  ;  Jing Wen  ;  Seung Woo Park  ;  Byungkyu Park  ;  Chang-Woo Gham  ;  Woo Jin Hyung  ;  Sung Hoon Noh  ;  Ho Kun Kim  ;  Si Young Song 
Citation
 Mutation Research, Vol.578(1~2) : 187-201, 2005 
Journal Title
 Mutation Research 
ISSN
 0027-5107 
Issue Date
2005
Abstract
Since the underlying mechanism for the high incidence of aneuploidy in gastric cancer has not clarified, we screened 49 gastric cancers and five gastric cancer cell lines for mutations in the mitotic spindle checkpoint genes, Bub1 and Mad2, and we analyzed the functional consequences of these mutations. The presence of mutations in Bub1 and Mad2 coding sequences was primarily detected by RT-PCR–SSCP and subsequently confirmed by automatic sequencing of either the RT-PCR products and/or the PCR products from genomic DNA. Mad2 was mutated in 44.9% of gastric cancer tissues and one gastric cancer cell line, N87, but not Bub1. Of these, three mutational hotspots at codons 156, 165 and 182 were identified. Mutations at codons 165 and 182 led to amino acid substitutions, whereas the mutation at codon 156 was a silent one. Overexpression of mutant Mad2 in HeLa cells led to the appearance of aneuploid cells in the presence of nocodazole, and this indicated that these mutations caused a defect in MAD2 protein. Wild type and mutant MAD2 protein displayed distinct mobility on two-dimensional gel electrophoresis. Novel mutational hotspots in human Mad2 genes were discovered for the gastric cancers and these mutations caused the functional defects in the spindle checkpoint suggesting that these mutations might be involved in the development and progression of gastric cancer.
Full Text
http://www.sciencedirect.com/science/article/pii/S0027510705003635
DOI
10.1016/j.mrfmmm.2005.05.020
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sun A(김선아) ORCID logo https://orcid.org/0000-0002-7174-3640
Kim, Chang Woo(김창우)
Kim, Han Soo(김한수)
Kim, Ho Keun(김호근)
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Wen, Jing(문정)
Park, Byung Kyu(박병규)
Park, Soo Bin(박수빈)
Park, Seung Woo(박승우) ORCID logo https://orcid.org/0000-0001-8230-964X
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Hyung, Woo Jin(형우진) ORCID logo https://orcid.org/0000-0002-8593-9214
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/150006
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