Frequent splicing aberration of the base excision repair gene hMYH in human gastric cancer.
BACKGROUND
Missense mutation of hMYH, which prevents transversion mutations induced by oxidative DNA damage, is reportedly associated with the development of gastric and colon cancer. We investigated whether deficiency or mutation of hMYH is associated with gastric carcinogenesis.


METHODS
Thirty patients with gastric carcinoma, three gastric cancer cell lines and lymphocytes from three healthy volunteers were investigated. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for hMYH, and the full-length sequence of hMYH mRNA was analysed.


RESULTS
A silent mutation at codon 473 was seen in two tumours. Single nucleotide polymorphism at codon 345 was observed in 14 patients. These two base substitutions had no pathogenic effect. Seven splice variants were observed and two aberrant transcripts were detected more frequently in cancer specimens (67%) than in normal mucosa (10%).


CONCLUSIONS
The high frequency of splicing aberration in cancer tissues suggests that aberrant transcripts may be involved in gastric carcinogenesis and cancer development.
Kobayashi
Katsutoshi
K
Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan. caseysurg@violin.ocn.ne.jp
Shida
Atsuo
A
Yamada
Hisashi
H
Ishibashi
Yoshio
Y
Nakayama
Ritsuko
R
Toriumi
Yasuo
Y
Mitsumori
Norio
N
Kashiwagi
Hideyuki
H
Yanaga
Katsuhiko
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D001483:Base Sequence; D003062:Codon; D045647:DNA Glycosylases / Q000096:biosynthesis / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics*
D003062:Codon; D012333:RNA, Messenger; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase