Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer

Pearlly S. Yan, Huidong Shi, Farahnaz Rahmatpanah, Timothy H C Hsiau, Andrew H A Hsiau, Yu Wei Leu, Joseph C. Liu, Hui-ming Huang

Research output: Contribution to journalArticle

103 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6178-6186
Number of pages9
JournalCancer Research
Volume63
Issue number19
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

CpG Islands
DNA Methylation
Methylation
Breast Neoplasms
Histones
Exons
Neoplasms
Oligonucleotides
Lysine
Genetic Epigenesis
Neoplastic Processes
Cell Line
Heterochromatin
Gene Silencing
Oligonucleotide Array Sequence Analysis
Epigenomics
Chromatin
Breast
Alleles

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yan, P. S., Shi, H., Rahmatpanah, F., Hsiau, T. H. C., Hsiau, A. H. A., Leu, Y. W., ... Huang, H. (2003). Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. Cancer Research, 63(19), 6178-6186.

Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. / Yan, Pearlly S.; Shi, Huidong; Rahmatpanah, Farahnaz; Hsiau, Timothy H C; Hsiau, Andrew H A; Leu, Yu Wei; Liu, Joseph C.; Huang, Hui-ming.

In: Cancer Research, Vol. 63, No. 19, 01.10.2003, p. 6178-6186.

Research output: Contribution to journalArticle

Yan, PS, Shi, H, Rahmatpanah, F, Hsiau, THC, Hsiau, AHA, Leu, YW, Liu, JC & Huang, H 2003, 'Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer', Cancer Research, vol. 63, no. 19, pp. 6178-6186.
Yan PS, Shi H, Rahmatpanah F, Hsiau THC, Hsiau AHA, Leu YW et al. Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. Cancer Research. 2003 Oct 1;63(19):6178-6186.
Yan, Pearlly S. ; Shi, Huidong ; Rahmatpanah, Farahnaz ; Hsiau, Timothy H C ; Hsiau, Andrew H A ; Leu, Yu Wei ; Liu, Joseph C. ; Huang, Hui-ming. / Differential distribution of DNA methylation within the RASSF1A CpG island in breast cancer. In: Cancer Research. 2003 ; Vol. 63, No. 19. pp. 6178-6186.
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