title: Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer.
abstract: DNA methylation is the main epigenetic modification that occurs at the early stages of carcinogenesis. We performed a genome-wide DNA methylation profiling to evaluate whether the DNA methylation state is different in the estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. Twelve ER+/PR+ and 12 ER-/PR- breast cancer tissues were selected from the biorepository of the Seoul Breast Cancer Study for Infinium Methylation Assay. The difference of the DNA methylation state of 27 578 methylation sites in 14 000 genes between two groups was evaluated by Student's t-test. False discovery rate (FDR) was estimated to evaluate the probability of false positive associations. Of the 27 578 sites, 148 sites (0.54%) were significantly different between ER+/PR+ and ER-/PR- breast cancers (P < 0.001); 93 hypermethylated and 55 hypomethylated. Five genes, FAM124B (P = 7.26 × 10(-7)), MANEAL (P = 3.38 × 10(-7)), ST6GALNAC1 (P = 2.85 × 10(-6)), NAV1 (P = 5.94 × 10(-6)) and PER1 (P = 6.45 × 10(-6)) remained significant after correction for multiple tests (FDR < 0.05). In a subsequent replication study for five genes, four of the five genes were validated; FAM124B and ST6GALNAC1 were significantly hypermethylated, and NAV1 and PER1 were significantly hypomethylated in ER+/PR+ breast cancers (P < 0.05). In the first genome-wide DNA methylation profiling according to the receptor status of breast cancer, we found that ER/PR status affects the DNA methylation state of FAM124B, ST6GALNAC1, NAV1 and PER1 in breast cancer.
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Lian
authors: L
authors: Li
authors: Kyoung-Mu
authors: KM
authors: Lee
authors: Wonshik
authors: W
authors: Han
authors: Ji-Yeob
authors: JY
authors: Choi
authors: Ji-Young
authors: JY
authors: Lee
authors: Gyeong Hoon
authors: GH
authors: Kang
authors: Sue Kyung
authors: SK
authors: Park
authors: Dong-Young
authors: DY
authors: Noh
authors: Keun-Young
authors: KY
authors: Yoo
authors: Daehee
authors: D
authors: Kang
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016612:Paraffin Embedding; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone