title: Aberrant methylation of the maspin promoter is an early event in human breast cancer.
abstract: The maspin gene functions as a tumor suppressor in human breasts, and its expression is frequently lost during breast cancer progression. In vitro models of human breast cancer indicate that the loss of maspin expression is closely linked to aberrant methylation of the maspin promoter. We conducted a study on 30 archival ductal carcinoma in situ (DCIS) specimens to determine if aberrant methylation of the maspin promoter occurred in vivo, and whether it occurred early in breast cancer evolution. Healthy tissue obtained from reduction mammoplasty was used as normal control. Results from immunohistochemical analysis indicate that maspin expression is lost in a substantial fraction of DCIS specimens (57%). Bisulfite sequencing of DNA isolated from laser capture-microdissected normal and neoplastic ducts showed that loss of maspin expression was often, but not always, linked to aberrant methylation of the maspin promoter, suggesting that other mechanisms, in addition to aberrant methylation, participate and/or cooperate to silence maspin gene expression. Taken together, these results indicate that aberrant methylation of the maspin promoter is an early event in human breast cancer.
authors.affiliation: Bone Marrow Transplant Program, Arizona Cancer Center, and Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85724, USA. bfutscher@azcc.arizona.edu
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Futscher
authors.forename: Megan M
authors.initials: MM
authors.lastname: O'Meara
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Rennels
authors.forename: Di
authors.initials: D
authors.lastname: Lu
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Gruman
authors.forename: Richard E B
authors.initials: RE
authors.lastname: Seftor
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Domann
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D015843:Serpins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins