A similar cell-specific pattern of HOXA methylation in normal and in cancer tissues

作者：Avraham Ayelet^*; Sandbank Judith; Yarom Nirit; Shalom Avshalom; Karni Tami; Pappo Itzhak; Sella Avishay; Fich Alexander; Walfisch Shlomo; Gheber Larisa; Evron Ella

来源：Epigenetics, 2010, 5(1): 41-46.

DOI：10.4161/epi.5.1.10724

• DNA methylation
• HOX genes
• breast cancer
• cell type specific methylation
• genome-wide methylation array

HOX genes are developmental genes that determine anterior-posterior embryonic pattern and govern the process of differentiation. Inappropriate expression of HOX genes has been implicated in developmental abnormalities and hematopoietic malignancies. In addition, HOX genes silencing by DNA methylation has been reported in cancers and related to disease aggressiveness and outcome. On the other hand, accumulating evidence suggests that epigenetic changes at HOX genes are linked to normal development and differentiation. To better understand the relationship between HOXA methylation and cancer, we analyzed the methylation pattern of HOXA genes in human primary breast and colon carcinomas, normal tissues, and normal white blood cells. Genome-wide methylation arrays of breast cancers and white blood cells demonstrated similar methylation patterns. Quantitative methylation analysis of seven representative HOXA genes revealed various levels of methylation in both normal tissues and cancers. Analysis of epithelial-enriched normal breast tissue and stroma indicated that the stroma was the major origin of HOXA methylation. Furthermore, in selected dense breast cancers, minimal increase in methylation of several HOXA genes did not correlate with the predominance of malignant epithelial cells in these tumors. Our results suggest that methylation of the HOXA cluster may be a normal developmental and cell type specific process rather than a cancer specific mechanism.

• 出版日期2010-1-1