Tags

Type your tag names separated by a space and hit enter

Accumulation of DNA methylation is associated with tumor stage in gastric cancer.
Cancer. 2006 Mar 15; 106(6):1250-9.C

Abstract

BACKGROUND

The authors purpose in this study was to clarify the difference in terms of clinicopathologic features between gastric cancer (GC) with high numbers of DNA methylated genes and CpG island methylator phenotype (CIMP)-positive GC as originally defined.

METHODS

We analyzed DNA methylation of 12 tumor-related genes (hMLH1, MGMT, p16(INK4a), CDH1, RAR-beta, HLTF, RIZ1, TM, FLNc, LOX, HRASLS, HAND1) in 75 samples of GC from 75 patients, 25 samples of corresponding nonneoplastic mucosa from 25 patients, and 10 samples of normal gastric mucosa from 10 healthy young individuals by methylation-specific polymerase chain reaction (PCR) and bisulfite PCR. We also investigated CIMP status by examining the methylation of five MINT loci and p53 mutation status by PCR single-strand conformation polymorphism. We measured levels of expression of mRNAs for these 12 genes by quantitative reverse transcription PCR in 50 GC specimens.

RESULTS

The average number of methylated genes per tumor was 4.83. DNA methylation of each gene was correlated with low expression of the respective mRNA. High methylation (GC with 5 or more methylated genes) was detected in 39 (52.0%) of 75 GCs. Twenty-nine (37.8%) of 75 GCs were CIMP-positive. DNA methylation of each of the 12 genes was observed more frequently in the high-methylation group than in the low-methylation group. Methylation of 6 specific genes occurred more frequently in CIMP-positive GC than in CIMP-negative GC. Methylation of the remaining 6 genes was not correlated with CIMP-status. High methylation was found more frequently in Stage III/IV GC (26 of 40 cases, 65.0%) than in Stage I/II GC (13 of 35 cases, 37.1%, P = 0.029).CONCLUSIONS.These findings indicate that GCs with higher numbers of methylated genes have more distinct DNA methylation profiles than the originally defined CIMP-positive GCs. DNA methylation of tumor-related genes accumulates in conjunction with tumor progression.

Authors+Show Affiliations

Department of Molecular Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16475210

Citation

Oue, Naohide, et al. "Accumulation of DNA Methylation Is Associated With Tumor Stage in Gastric Cancer." Cancer, vol. 106, no. 6, 2006, pp. 1250-9.
Oue N, Mitani Y, Motoshita J, et al. Accumulation of DNA methylation is associated with tumor stage in gastric cancer. Cancer. 2006;106(6):1250-9.
Oue, N., Mitani, Y., Motoshita, J., Matsumura, S., Yoshida, K., Kuniyasu, H., Nakayama, H., & Yasui, W. (2006). Accumulation of DNA methylation is associated with tumor stage in gastric cancer. Cancer, 106(6), 1250-9.
Oue N, et al. Accumulation of DNA Methylation Is Associated With Tumor Stage in Gastric Cancer. Cancer. 2006 Mar 15;106(6):1250-9. PubMed PMID: 16475210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Accumulation of DNA methylation is associated with tumor stage in gastric cancer. AU - Oue,Naohide, AU - Mitani,Yoshitsugu, AU - Motoshita,Junichi, AU - Matsumura,Shunji, AU - Yoshida,Kazuhiro, AU - Kuniyasu,Hiroki, AU - Nakayama,Hirofumi, AU - Yasui,Wataru, PY - 2006/2/14/pubmed PY - 2006/5/5/medline PY - 2006/2/14/entrez SP - 1250 EP - 9 JF - Cancer JO - Cancer VL - 106 IS - 6 N2 - BACKGROUND: The authors purpose in this study was to clarify the difference in terms of clinicopathologic features between gastric cancer (GC) with high numbers of DNA methylated genes and CpG island methylator phenotype (CIMP)-positive GC as originally defined. METHODS: We analyzed DNA methylation of 12 tumor-related genes (hMLH1, MGMT, p16(INK4a), CDH1, RAR-beta, HLTF, RIZ1, TM, FLNc, LOX, HRASLS, HAND1) in 75 samples of GC from 75 patients, 25 samples of corresponding nonneoplastic mucosa from 25 patients, and 10 samples of normal gastric mucosa from 10 healthy young individuals by methylation-specific polymerase chain reaction (PCR) and bisulfite PCR. We also investigated CIMP status by examining the methylation of five MINT loci and p53 mutation status by PCR single-strand conformation polymorphism. We measured levels of expression of mRNAs for these 12 genes by quantitative reverse transcription PCR in 50 GC specimens. RESULTS: The average number of methylated genes per tumor was 4.83. DNA methylation of each gene was correlated with low expression of the respective mRNA. High methylation (GC with 5 or more methylated genes) was detected in 39 (52.0%) of 75 GCs. Twenty-nine (37.8%) of 75 GCs were CIMP-positive. DNA methylation of each of the 12 genes was observed more frequently in the high-methylation group than in the low-methylation group. Methylation of 6 specific genes occurred more frequently in CIMP-positive GC than in CIMP-negative GC. Methylation of the remaining 6 genes was not correlated with CIMP-status. High methylation was found more frequently in Stage III/IV GC (26 of 40 cases, 65.0%) than in Stage I/II GC (13 of 35 cases, 37.1%, P = 0.029).CONCLUSIONS.These findings indicate that GCs with higher numbers of methylated genes have more distinct DNA methylation profiles than the originally defined CIMP-positive GCs. DNA methylation of tumor-related genes accumulates in conjunction with tumor progression. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/16475210/Accumulation_of_DNA_methylation_is_associated_with_tumor_stage_in_gastric_cancer_ L2 - https://doi.org/10.1002/cncr.21754 DB - PRIME DP - Unbound Medicine ER -