Microarray-based survey of CpG islands identifies concurrent hyper- and hypomethylation patterns in tissues derived from patients with breast cancer

Piotrowski, Arkadiusz, Benetkiewicz, Magdalena, Menzel, Uwe, de Ståhl, Teresita Díaz, Mantripragada, Kiran Kumar ORCID: https://orcid.org/0000-0003-2070-8105, Grigelionis, Gintautas, Buckley, Patrick G., Jankowski, Michal, Hoffman, Jacek, Bala, Dariusz, Srutek, Ewa, Laskowski, Ryszard, Zegarski, Wojciech and Dumanski, Jan P. 2006. Microarray-based survey of CpG islands identifies concurrent hyper- and hypomethylation patterns in tissues derived from patients with breast cancer. Genes, Chromosomes and Cancer 45 (7) , pp. 656-657. 10.1002/gcc.20331

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Abstract

Maintenance of CpG island methylation in the genome is crucial for cellular homeostasis and this balance is disrupted in cancer. Our rationale was to compare the methylation of CpG islands in tissues (tumor, healthy breast and blood) from patients with breast cancer. We studied 72 genes in 103 samples using microarray hybridization and bisulfite sequencing. We observed tumor specific hyper- or hypomethylation of five genes; COL9A1, MT1A, MT1J, HOXA5 and FLJ45983. A general drop of methylation in COL9A1 was apparent in tumors, when compared with blood and healthy breast tissue. Furthermore, one tumor displayed a complete loss of methylation of all five genes, suggesting overall impairment of methylation. The downstream, evolutionary conserved island of HOXA5 showed hypomethylation in 18 tumors and complete methylation in others. This CpG island also displayed a semimethylated state in the majority of normal breast samples, when compared to complete methylation in blood. Distinct methylation patterns were further seen in MT1J and MT1A, belonging to the metallothionein gene family. The CpG islands of these genes are spaced by 2 kb, which shows selective methylation of two structurally and functionally related genes. The promoters of FLJ45983 and MT1A were methylated above 25% in 18 primary and metastatic tumors. Concurrently, there was also >10% methylation of healthy breast tissue in 11 and 5 samples, respectively. This suggests that the methylation process for the latter two genes takes place already in normal breast cells. Our results also point to a considerable heterogeneity of epigenetic disturbance in breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Wiley-Liss Inc
ISSN:	1045-2257
Last Modified:	31 Oct 2022 09:46
URI:	https://orca.cardiff.ac.uk/id/eprint/82414

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