Genetic alterations of the MYH gene in gastric cancer.
Increased oxygen free radicals produced in gastric mucosa by H. pylori induce DNA damage and lead to dyspalsia and gastric cancers. However, only a small percentage of individuals that carry H. pylori develop gastric cancer, indicating that other factors are involved. We have screened a set of 95 sporadic gastric cancers for mutations and allele loss of the DNA glycosylase MYH gene, which excises adenine misincorporated opposite unrepaired 8-oxoG. Two of 95 cancers had bi-allelic mutations of the MYH gene with somatic missense mutation of one allele and loss of the remaining allele. The mutations were missense mutations, P391S and Q400R, in exon 13 encoding NUDIX hydrolase domain of the gene. The patients were H. pylori-positive and the tumors were of advanced intestinal-type gastric cancer with lymph node metastasis. In addition, 4 (17.4%) of 23 informative cases showed allele loss at MYH locus. Therefore, our data suggest that somatic mutations of base excision repair gene MYH contribute to the development of a sub-set of sporadic gastric cancers.
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
Chang Jae
CJ
Kim
Yong Gu
YG
Cho
Cho Hyun
CH
Park
Su Young
SY
Kim
Suk Woo
SW
Nam
Sug Hyung
SH
Lee
Nam Jin
NJ
Yoo
Jung Young
JY
Lee
Won Sang
WS
Park
D019943:Amino Acid Substitution; D045647:DNA Glycosylases / Q000235:genetics*; D005091:Exons; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D009154:Mutation; D020125:Mutation, Missense; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D045647:DNA Glycosylases; C061738:mutY adenine glycosylase