CPG METHYLATION WITHIN THE 5'-REGULATORY REGION OF THE BRCA1 GENE IS TUMOR-SPECIFIC AND INCLUDES A PUTATIVE CREB BINDING-SITE

Citation
Dn. Mancini et al., CPG METHYLATION WITHIN THE 5'-REGULATORY REGION OF THE BRCA1 GENE IS TUMOR-SPECIFIC AND INCLUDES A PUTATIVE CREB BINDING-SITE, Oncogene, 16(9), 1998, pp. 1161-1169
Citations number
41
Categorie Soggetti
Oncology,Biology,"Cell Biology","Genetics & Heredity
Journal title
ISSN journal
09509232
Volume
16
Issue
9
Year of publication
1998
Pages
1161 - 1169
Database
ISI
SICI code
0950-9232(1998)16:9<1161:CMWT5R>2.0.ZU;2-N
Abstract
Breast cancer is a genetic disease arising from a series of germ-line and/or somatic DNA changes in a variety of genes, including BRCA1 and BRCA2, DNA modifications have been shown to occur by a number of mecha nisms that include DNA methylation, In some cases, the aberrant methyl ation of CpGs within 5' regulatory regions has led to suppression of g ene activity. In this report we describe a variation in the pattern of DNA methylation within the regulatory region of the BRCA1 gene, We fo und no evidence of methylation at CpGs within the BRCA1 promoter in a variety of normal human tissues, However, screening of a series of ran domly sampled breast carcinomas revealed the presence of CpG methylati on adjacent to the BRCA1 transcription start site. One such methylated CpG occurs at a putative CREB (cAMP-responsive element binding) trans cription factor binding site in the BRCA1 promoter, Gelshift assays wi th methylated and unmethylated BRCA1/CREB binding site oligonucleotide s demonstrate that this site is sensitive to site-specific CpG methyla tion, These data suggest that aberrant DNA methylation at regulatory s equences in the BRCA1 locus may play a role in the transcriptional ina ctivation of the BRCA1 gene within subclones of breast tumors, This st udy represents the first evidence suggesting a role for DNA methylatio n in the transcriptional inactivation of the BRCA1 in human breast can cer.