title: Microsatellite instability is uncommon in breast cancer.
abstract: In some tumors, defects in mismatch repair enzymes lead to errors in the replication of simple nucleotide repeat segments. This condition is commonly known as microsatellite instability (MSI) because of the frequent mutations of microsatellite sequences. Although the MSI phenotype is well recognized in some colon, gastric, pancreatic, and endometrial cancers, reports of MSI in breast cancer are inconsistent. We report here our experience with >10,000 amplifications of simple nucleotide repeats in noncoding genomic regions using DNA from 267 cases of breast cancer, including cases that represent all major histological types of breast cancer. We rarely (10 reactions) found unexpected bands in amplifications of tumor DNA that were not present in amplifications of normal DNA. Moreover, repeats of these reactions did not confirm microsatellite instability in a single case. We also evaluated the simple nucleotide repeats in the transforming growth factor type II receptor, insulin-like growth factor type II receptor, BAX, and E2F-4 genes, which are frequently mutated in tumors with microsatellite instability. No mutations of these genes were found in any of the 30 breast cancer cell lines and 61 primary breast cancer samples examined. These results indicate that mismatch repair errors characteristic of the MSI phenotype are uncommon in human breast cancer.
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
authors.forename: R
authors.initials: R
authors.lastname: Anbazhagan
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.forename: E
authors.initials: E
authors.lastname: Gabrielson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050704:E2F4 Transcription Factor; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II