Abstract:
:We previously identified a polymorphism in the human estrogen receptor (ER) gene, within the coding region for the protein's amino terminal B-domain. In estrogen receptor-positive (ER+) breast tumors, the variant allele was preferentially associated with lower levels of ER, and was clinically correlated with frequent spontaneous abortions. DNA sequencing revealed a point mutation that changes codon 86 from Ala to Val and a silent mutation in codon 87. Because we initially detected the variant allele by analyzing RNA, only those tissues in which the ER gene is actively expressed were suitable for genotype analysis. We now describe an assay that uses genomic DNA as the substrate for determining the ER B genotype, DNA containing the polymorphic region of the ER gene is amplified by the polymerase chain reaction, then the amplified DNA is hybridized with radiolabeled oligonucleotide probes complementary to the wild type and variant ER alleles. This method allowed us to determine the ER B genotype of women with ER+ and ER- tumors, starting with minute amounts of DNA from frozen or paraffin embedded tissues. ER B genotyping was also performed on women without breast cancer using DNA extracted from blood cells. The combined results from analyses of RNA and DNA from 300 breast cancer patients showed that 12% were heterozygotes. In the ER+ group (n = 183), 11.5% carried the variant gene compared to 12.8% in the ER-negative group (n = 117) (chi 2 = 0.11; df = 1; p greater than 0.25).(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Schmutzler RK,Sanchez M,Lehrer S,Chaparro CA,Phillips C,Rabin J,Schachter Bdoi
10.1007/BF01980941subject
Has Abstractpub_date
1991-10-01 00:00:00pages
111-7issue
2eissn
0167-6806issn
1573-7217journal_volume
19pub_type
杂志文章abstract::A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. Results of these studies indicate local gray matter volume decrease and an increase in white matter lesions. Up till now, it ...
journal_title:Breast cancer research and treatment
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