Quantitative assessment of gene methylation in neoplastic and non-neoplastic gastric epithelia using methylation-specific DNA microarray.
A fiber-type DNA microarray was used to calculate methylation rates (MR) of four tumor suppressor genes, lysyl oxidase (LOX), p16, RUNX3, and tazarotene-induced gene 1 (TIG1). MR were calculated in 26 primary gastric cancers and corresponding non-neoplastic gastric epithelia, and the results were compared to those of conventional methylation-specific polymerase chain reaction (MSP). MR ranged from 0.1% to 69.1% (mean, 18.3%) for LOX, 0.5-74.1% (mean, 15.7%) for p16, 0.2-76.5% (mean, 22.7%) for RUNX3, and 0.6-41.2% (mean, 5.8%) for TIG1 in primary gastric cancers, and from 0.1% to 25.8% (mean, 8.7%) for LOX, 1.0- 23.2% (mean, 10.3%) for p16, 0.7-25.1% (mean, 5.5%) for RUNX3, and 1.8-27.6% (mean, 11.4%) for TIG1 in corresponding non-neoplastic gastric epithelia. Although MR varied significantly across different samples for both neoplastic and non-neoplastic gastric epithelia, high-level methylation (MR >40%) was cancer specific and was observed in 19.2%, 19.2%, 30.8%, and 3.8% of primary gastric cancers for LOX, p16, RUNX3, and TIG1, respectively. All samples with high-level methylation, as well as some samples with low MR (particularly <10%) were judged to be methylation positive on conventional MSP. Quantitative analysis of gene methylation using methylation-specific DNA microarray is a promising method for cancer diagnosis.
Tamura
Gen
G
Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan. gtamura@ypch.gr.jp
So
Kanji
K
Miyoshi
Hiroaki
H
Honda
Teiichiro
T
Nishizuka
Satoshi
S
Motoyama
Teiichi
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics*