title: Downregulation of EphA7 by hypermethylation in colorectal cancer.
abstract: A significant reduction of EphA7 expression in human colorectal cancers was shown using semiquantitative reverse transcription-polymerase chain reaction analysis in 59 colorectal cancer tissues, compared to corresponding normal mucosas (P=0.008), and five colon cancer cell lines. To investigate the mechanism of EphA7 downregulation in colorectal cancer, we examined the methylation status of the 5'CpG island around the translation start site in five colon cancer cell lines using restriction enzymes, methylation-specific PCR, and bisulfite sequencing and found evidence of aberrant methylation. The expression of EphA7 in colon cancer cell lines was restored after treatment with 5-aza-2'-deoxycytidine. Analysis of methylation status in totally 75 tumors compared to clinicopathological parameters revealed that hypermethylation of colorectal cancers was more frequent in male than in female (P=0.0078), and in moderately differentiated than in well-differentiated adenocarcinomas (P=0.0361). There was a tendency that hypermethylation in rectal cancers was more frequent than in colon cancers (P=0.0816). Hypermethylation was also observed in colorectal adenomas. This is the first report describing the downregulation of an Eph family gene in a solid tumor via aberrant 5'CpG island methylation. It provides the evidence that EphA7 gene is involved in human colorectal carcinogenesis.
authors: Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors: Jiandong
authors: J
authors: Wang
authors: Hideki
authors: H
authors: Kataoka
authors: Masaya
authors: M
authors: Suzuki
authors: Naomi
authors: N
authors: Sato
authors: Ritsuko
authors: R
authors: Nakamura
authors: Hong
authors: H
authors: Tao
authors: Keiji
authors: K
authors: Maruyama
authors: Jun
authors: J
authors: Isogaki
authors: Shigeru
authors: S
authors: Kanaoka
authors: Megumi
authors: M
authors: Ihara
authors: Masamitsu
authors: M
authors: Tanaka
authors: Masao
authors: M
authors: Kanamori
authors: Toshio
authors: T
authors: Nakamura
authors: Kazuya
authors: K
authors: Shinmura
authors: Haruhiko
authors: H
authors: Sugimura
mesh_terms: D000368:Aged; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D036141:Receptor, EphA7 / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D012333:RNA, Messenger; D036141:Receptor, EphA7