Mapping of ER gene CpG island methylation-specific polymerase chain reaction.
Southern analysis has shown that DNA from 25% of primary estrogen receptor (ER) alpha-negative breast tumors displays aberrant methylation at one site within the ER gene CpG island. To examine more sites and increase sensitivity, we developed a methylation-specific PCR assay to map methylation of the entire ER CpG island. The island was unmethylated in normal breast tissue and ER-positive breast cancer cell lines, but extensively methylated in all ER-negative cell lines and breast tumors examined. In addition, some of the ER-positive/progesterone receptor-negative and ER-positive/progesterone receptor-positive tumors (about 70% and 35%, respectively) displayed methylation of the ER CpG island, suggesting that this heterogeneity within tumor cell populations could potentially shed light on the etiology of ER-negative recurrent tumors arising from ER-positive tumors.
Lapidus
R G
RG
Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Nass
S J
SJ
Butash
K A
KA
Parl
F F
FF
Weitzman
S A
SA
Graff
J G
JG
Herman
J G
JG
Davidson
N E
NE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011960:Receptors, Estrogen / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005819:Genetic Markers; D011960:Receptors, Estrogen