Estrogen receptor alpha mutation (A-to-G transition at nucleotide 908) is not found in different types of breast lesions from Japanese women.
BACKGROUND
An estrogen receptor (ER) alpha variant with an A-to-G transition at nucleotide 908 (A908G) has been identified in typical hyperplastic mammary epithelium. This somatic mutation, which induces a Lys-to-Arg substitution at residue 303 within exon 4 at the border of the hinge and hormone-binding domains of the ER alpha, shows increased sensitivity to estrogen compared with wild-type ER alpha.


METHODS
To investigate whether this mutation was present in breast lesions, we performed mutation analyses using the PCR-restriction fragment length polymorphism (RFLP) method in 7 cases of hyperplasia, 18 cases of benign breast tumor, 26 cases of ductal carcinoma in situ (DCIS) and 215 cases of invasive ductal carcinoma (IDC). When we extracted DNA, the hyperplastic epithelium and cancer cells of DCIS were microdissected. We also performed direct sequencing analysis from 7 randomly-selected representative cases of hyperplasia, 9 cases of benign breast tumors, 11 cases of DCIS and 20 cases of IDC.


RESULTS
No A908G mutation was found in the ER alpha gene in these breast lesions.


CONCLUSIONS
This mutation might be absent or occur in so few cells as to be undetectable by PCR-RFLP or direct sequencing.
Zhang
Zhenhuan
Z
Second Department of Surgery, Nagoya City University Medical School, Japan.
Yamashita
Hiroko
H
Toyama
Tatsuya
T
Omoto
Yoko
Y
Sugiura
Hiroshi
H
Hara
Yasuo
Y
Haruki
Nobuhiro
N
Kobayashi
Shunzo
S
Iwase
Hirotaka
H
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001941:Breast Diseases / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics*; D017422:Sequence Analysis, DNA
D011960:Receptors, Estrogen