Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer.
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.
Li
Lian
L
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
Lee
Kyoung-Mu
KM
Han
Wonshik
W
Choi
Ji-Yeob
JY
Lee
Ji-Young
JY
Kang
Gyeong Hoon
GH
Park
Sue Kyung
SK
Noh
Dong-Young
DY
Yoo
Keun-Young
KY
Kang
Daehee
D
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*
D017931:DNA Primers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone