Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays

P. S. Yan, C. M. Chen, H. Shi, F. Rahmatpanah, S. H. Wei, C. W. Caldwell, Hui-ming Huang

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

It is now clear that aberrant DNA methylation observed in cancer cells is not restricted to a few CpG islands, but affects multiple loci. When this epigenetic event occurs at the 5′-end of the regulatory region of genes, it is frequently associated with transcriptional silencing. To investigate further this widespread event in the tumor genome, we developed a novel microarray containing 7776 short GC-rich tags tethered to glass slide surfaces. This DNA chip was used to study 17 paired tissues of breast tumors and normal controls. Amplicons, representing differential pools of methylated DNA fragments between tumors and normal controls, were cohybridized to the microarray panel. Hypermethylation of multiple CpG island loci was then detected in a two-color fluorescence system. Approximately 1% (on average, 83 loci) of these CpG islands examined were hypermethylated in this patient group. Hierarchical clustering segregated these tumors based on their methylation profiles and identified a group of CpG island loci that corresponds to the hormone-receptor status of breast cancer. This observation was independently confirmed by examining a single locus, the promoter of the human glypican 3 gene, which was predominate]y hypermethylated in the hormone receptor-negative tumors. Our findings support the notion that hypermethylation of critical CpG island loci influences cancer development and produces distinct epigenetic signatures for particular tumor subtypes.

Original languageEnglish (US)
Pages (from-to)8375-8380
Number of pages6
JournalCancer Research
Volume61
Issue number23
StatePublished - Dec 1 2001
Externally publishedYes

Fingerprint

CpG Islands
Epigenomics
Breast Neoplasms
Neoplasms
Glypicans
Hormones
Nucleic Acid Regulatory Sequences
DNA Methylation
Regulator Genes
Oligonucleotide Array Sequence Analysis
Methylation
Glass
Cluster Analysis
Color
Fluorescence
Genome
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yan, P. S., Chen, C. M., Shi, H., Rahmatpanah, F., Wei, S. H., Caldwell, C. W., & Huang, H. (2001). Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays. Cancer Research, 61(23), 8375-8380.

Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays. / Yan, P. S.; Chen, C. M.; Shi, H.; Rahmatpanah, F.; Wei, S. H.; Caldwell, C. W.; Huang, Hui-ming.

In: Cancer Research, Vol. 61, No. 23, 01.12.2001, p. 8375-8380.

Research output: Contribution to journalArticle

Yan, PS, Chen, CM, Shi, H, Rahmatpanah, F, Wei, SH, Caldwell, CW & Huang, H 2001, 'Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays', Cancer Research, vol. 61, no. 23, pp. 8375-8380.
Yan PS, Chen CM, Shi H, Rahmatpanah F, Wei SH, Caldwell CW et al. Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays. Cancer Research. 2001 Dec 1;61(23):8375-8380.
Yan, P. S. ; Chen, C. M. ; Shi, H. ; Rahmatpanah, F. ; Wei, S. H. ; Caldwell, C. W. ; Huang, Hui-ming. / Dissecting complex epigenetic alterations in breast cancer using CpG island microarrays. In: Cancer Research. 2001 ; Vol. 61, No. 23. pp. 8375-8380.
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