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Sporadic breast cancer patients' germline DNA exhibit an AT‐rich microsatellite signature
Author(s) -
Galindo Cristi L.,
McIver Lauren J.,
Tae Hongseok,
McCormick John F.,
Skinner Michael A.,
Hoeschele Ina,
Lewis Cheryl M.,
Minna John D.,
Boothman David A.,
Garner Harold R.
Publication year - 2011
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20853
Subject(s) - microsatellite , germline , biology , breast cancer , cancer , microsatellite instability , genetics , cancer research , germline mutation , colorectal cancer , mutation , gene , allele
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. © 2011 Wiley‐Liss, Inc.