title: Sporadic breast cancer patients' germline DNA exhibit an AT-rich microsatellite signature.
abstract: Using a custom CGH-like oligonucleotide array to measure the global microsatellite content in the genomes of 72 cancer, cancer-free, and high risk patient and cell line samples (56 germline DNA and 16 in tumor or tumor cell line DNA) we found a unique, reproducible, and statistically significant pattern of 18 motif-specific microsatellite families (out of 962 possible 1-6 mer repeats) in breast cancer patient germline and tumor DNA, but not in germline DNA of cancer-free volunteer controls or in breast cancer patients with BRCA1/2 mutations. These high-similarity A/T rich repetitive motifs were also more pronounced in the germlines and tumors of colon cancer tumor patients (3/6 samples) and microsatellite unstable colon cancer cell lines; however, germline DNA of sporadic breast cancer patients exhibited the largest global content shift for those motifs with extreme AT/GC ratios. These results indicate that global microsatellite variability is complex, suggest the existence of a previously unknown genomic destabilization mechanism in breast cancer patients' germline DNA, and warrant further testing of such microsatellite variability as a predictor of future breast cancer development.
authors.affiliation: Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0477, USA.
authors.forename: Cristi L
authors.initials: CL
authors.lastname: Galindo
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: McIver
authors.forename: Hongseok
authors.initials: H
authors.lastname: Tae
authors.forename: John F
authors.initials: JF
authors.lastname: McCormick
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skinner
authors.forename: Ina
authors.initials: I
authors.lastname: Hoeschele
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Lewis
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: David A
authors.initials: DA
authors.lastname: Boothman
authors.forename: Harold R
authors.initials: HR
authors.lastname: Garner
mesh_terms: D020856:AT Rich Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D014644:Genetic Variation; D006801:Humans; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
chemical_list: D004273:DNA, Neoplasm