title: Distinct genetic and epigenetic changes in medullary breast cancer.
abstract: Genetic instability resulting in chromosome aneuploidy or mismatch repair deficiency characterizes cancer. Medullary carcinoma (MC) of the breast is a specific form of breast cancer with unique clinical, epidemiologic, and prognostic features, suggesting distinctive tumorigenic pathways. To investigate the nature of the genetic changes associated with MC we analyzed a series of 22 tumors. Chromosomal imbalances were assessed by comparative genomic hybridization (CGH) and mismatch repair (MMR) deficiency tested for through assessment of microsatellite instability (MSI) and expression of MLH1 and MSH2 genes. MMR deficiency was detected in only a small proportion of cases. The chromosomal copy number changes showed some similarities to BRCA1-associated tumors. A high level of BRCA1 promoter hypermethylation was detected, suggesting a possible role of this gene in MC development.
authors.affiliation: Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, UK.
authors.forename: P
authors.initials: P
authors.lastname: Osin
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Lu
authors.forename: J
authors.initials: J
authors.lastname: Stone
authors.forename: T
authors.initials: T
authors.lastname: Crook
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
authors.forename: M
authors.initials: M
authors.lastname: Gasco
authors.forename: B A
authors.initials: BA
authors.lastname: Gusterson
authors.forename: J
authors.initials: J
authors.lastname: Shipley
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D004268:DNA-Binding Proteins; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins; D009693:Nucleic Acid Hybridization; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein