TY - JOUR
T1 - A similar cell-specific pattern of HOXA methylation in normal and in cancer tissues
AU - Avraham, Ayelet
AU - Sandbank, Judith
AU - Yarom, Nirit
AU - Shalom, Avshalom
AU - Karni, Tami
AU - Pappo, Itzhak
AU - Sella, Avishay
AU - Fich, Alexander
AU - Walfisch, Shlomo
AU - Gheber, Larisa
AU - Evron, Ella
N1 - Funding Information:
This study was supported by the Israeli Cancer Association grant no. C20070015 and partially by ISF grant no. 1043/09 and BSF grant no. 2003141 awarded to L.G.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Cell type specific methylation
KW - DNA methylation
KW - Genome-wide methylation array
KW - HOX genes
UR - http://www.scopus.com/inward/record.url?scp=77449087922&partnerID=8YFLogxK
U2 - 10.4161/epi.5.1.10724
DO - 10.4161/epi.5.1.10724
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AN - SCOPUS:77449087922
SN - 1559-2294
VL - 5
SP - 41
EP - 46
JO - Epigenetics
JF - Epigenetics
IS - 1
ER -