Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background non‐cancerous gastric mucosae

• Published in: Cancer science 2007-12, Vol.98 (12), p.1853-1861
• Main Authors: Enomoto, Shotaro, Maekita, Takao, Tsukamoto, Tetsuya, Nakajima, Takeshi, Nakazawa, Kazuyuki, Tatematsu, Masae, Ichinose, Masao, Ushijima, Toshikazu
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; CpG Islands - genetics; DNA Methylation; Female; Gastric Mucosa - pathology; Gastric Mucosa - physiology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Middle Aged; Original /Reports; Phenotype; Polymerase Chain Reaction; RNA, Viral - isolation & purification; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach Neoplasms - virology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2007.00625.x

The presence of high levels of aberrant DNA methylation in gastric mucosae correlates with risk of gastric cancer. Some gastric cancers are known to have methylation of multiple CpG islands (CGI), which is referred to as the CGI methylator phenotype (CIMP). In the present study, we aimed to clarify the possible association between the CIMP in cancers and high methylation levels in their background mucosae by accurate quantitative methylation analysis of 14 carefully selected promoter CGI. Methylation levels were measured in 66 cancers and their background mucosae, along with 19 normal mucosae of healthy volunteers. Methylation in cancers was classified as absent (methylation level = 0%) or positive. The number of methylated CGI in a cancer showed a continuous distribution, and cancers were classified as CIMP high (21 cases), CIMP low (30 cases), or CIMP negative (15 cases). CIMP‐high gastric cancer patients had significantly better survival rates than CIMP‐negative patients. Of the Epstein–Barr virus‐positive gastric cancers studied, eight out of nine presented as CIMP high. Methylation in background mucosae showed a unimodal distribution, and was assessed by their degree. The gastric mucosae of cancer patients showed higher levels than normal gastric mucosae of healthy volunteers. Finally, the CIMP‐high, CIMP‐low, and CIMP‐negative statuses in cancers were not associated with methylation levels of individual genes and their means in the background mucosae. These showed that the CIMP statuses in gastric cancers had no association with methylation levels in the background gastric mucosae. (Cancer Sci 2007; 98: 1853–1861)