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Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer.
Cancer Res. 2003 Oct 01; 63(19):6178-86.CR

Abstract

Aberrant DNA methylation of promoter CpG islands is associated with transcriptionally repressive heterochromatin in neoplasia. The dynamics of this epigenetic process in mediating the transition from an active to an inactive state of transcription remains to be elucidated, however. Here, we used the methylation-specific oligonucleotide microarray to map the methylation patterns of a CpG island, located within the promoter and the first exon regions of RASSF1A, in normal breast tissue controls, primary tumors, and breast cancer cell lines. Oligonucleotide pairs, spaced along the CpG island region, were designed to discriminate between methylated and unmethylated alleles of selected sites. The methylation-specific oligonucleotide data indicate that the majority of test samples show widespread methylation in the first exon of RASSF1A. In contrast, the promoter area was usually undermethylated in normal controls and in 32% of the primary tumors tested, whereas the rest of the primary tumors and breast cancer cell lines showed various degrees of methylation in the region. Methylation profiling of individual tumors further suggest that DNA methylation progressively spreads from the first exon into the promoter area of this gene. Functional analysis indicates that increased density of RASSF1A promoter methylation is associated with altered chromatin, marked by a depletion of acetylated histones and methylated histone 3-lysine 4 and an enrichment of methylated histone 3-lysine 9 in the studied area. The combination of these epigenetic modifications may engender a stable silencing of the gene in breast cancer cells. Thus, this study underscores the importance of detailed mapping of methylation patterns within a CpG island locus that may provide insights into the progressive nature of aberrant DNA methylation and its relationship with transcriptional silencing during the neoplastic process.

Authors+Show Affiliations

Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, 420 West 12th Avenue, Columbus, OH 43210, USA.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)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14559801

Citation

Yan, Pearlly S., et al. "Differential Distribution of DNA Methylation Within the RASSF1A CpG Island in Breast Cancer." Cancer Research, vol. 63, no. 19, 2003, pp. 6178-86.
Yan PS, Shi H, Rahmatpanah F, et al. Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. Cancer Res. 2003;63(19):6178-86.
Yan, P. S., Shi, H., Rahmatpanah, F., Hsiau, T. H., Hsiau, A. H., Leu, Y. W., Liu, J. C., & Huang, T. H. (2003). Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. Cancer Research, 63(19), 6178-86.
Yan PS, et al. Differential Distribution of DNA Methylation Within the RASSF1A CpG Island in Breast Cancer. Cancer Res. 2003 Oct 1;63(19):6178-86. PubMed PMID: 14559801.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. AU - Yan,Pearlly S, AU - Shi,Huidong, AU - Rahmatpanah,Farahnaz, AU - Hsiau,Timothy H-C, AU - Hsiau,Andrew H-A, AU - Leu,Yu-Wei, AU - Liu,Joseph C, AU - Huang,Tim Hui-Ming, PY - 2003/10/16/pubmed PY - 2003/12/4/medline PY - 2003/10/16/entrez SP - 6178 EP - 86 JF - Cancer research JO - Cancer Res VL - 63 IS - 19 N2 - Aberrant DNA methylation of promoter CpG islands is associated with transcriptionally repressive heterochromatin in neoplasia. The dynamics of this epigenetic process in mediating the transition from an active to an inactive state of transcription remains to be elucidated, however. Here, we used the methylation-specific oligonucleotide microarray to map the methylation patterns of a CpG island, located within the promoter and the first exon regions of RASSF1A, in normal breast tissue controls, primary tumors, and breast cancer cell lines. Oligonucleotide pairs, spaced along the CpG island region, were designed to discriminate between methylated and unmethylated alleles of selected sites. The methylation-specific oligonucleotide data indicate that the majority of test samples show widespread methylation in the first exon of RASSF1A. In contrast, the promoter area was usually undermethylated in normal controls and in 32% of the primary tumors tested, whereas the rest of the primary tumors and breast cancer cell lines showed various degrees of methylation in the region. Methylation profiling of individual tumors further suggest that DNA methylation progressively spreads from the first exon into the promoter area of this gene. Functional analysis indicates that increased density of RASSF1A promoter methylation is associated with altered chromatin, marked by a depletion of acetylated histones and methylated histone 3-lysine 4 and an enrichment of methylated histone 3-lysine 9 in the studied area. The combination of these epigenetic modifications may engender a stable silencing of the gene in breast cancer cells. Thus, this study underscores the importance of detailed mapping of methylation patterns within a CpG island locus that may provide insights into the progressive nature of aberrant DNA methylation and its relationship with transcriptional silencing during the neoplastic process. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/14559801/Differential_distribution_of_DNA_methylation_within_the_RASSF1A_CpG_island_in_breast_cancer_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=14559801 DB - PRIME DP - Unbound Medicine ER -