TY - JOUR
T1 - Microsatellite genotyping reveals a signature in breast cancer exomes
AU - McIver, L. J.
AU - Fonville, N. C.
AU - Karunasena, E.
AU - Garner, H. R.
N1 - Funding Information:
Acknowledgments This study was funded by the Virginia Bioin-formatics Institute Medical Informatics Systems Division director’s funds, the National Institute of Health, National Human Genome Research Institute, 1000 Genomes Project Dataset Analysis Grant (T-55818-363-1), and high performance computing was supported by a Grant from the National Science Foundation (OCI-1124123). This project was made possible through data provided by the 1000 Genomes Project and The Cancer Genome Atlas Project. The authors thank the system administrators in the VBI computational core (Michael Snow, Jeremy Johnson, Dominik Borkowski, David Bynum, Douglas McMaster, and Vedavyas Duggirala) for technical support. The authors would like to thank Hunt Willard for comments during the preparation of the manuscript. All the authors contributed to the experimental design, data analysis and the writing of this manuscript. In addition, L.J.M. designed, wrote, and ran all code, N.C.F. and E.K. provided biological interpretations, N.C.F. wrote the paper, and H.R.G. conceived and directed the study.
PY - 2014/6
Y1 - 2014/6
N2 - Genomic instability at microsatellite loci is a hallmark of many cancers, including breast cancer. However, much of the genomic variation and many of the hereditary components responsible for breast cancer remain undetected. We hypothesized that variation at microsatellites could provide additional genomic markers for breast cancer risk assessment. A total of 1,345 germline and tumor DNA samples from individuals diagnosed with breast cancer, exome sequenced as part of The Cancer Genome Atlas, were analyzed for microsatellite variation. The comparison group for our analysis, representing healthy individuals, consisted of 249 females which were exome sequenced as part of the 1,000 Genomes Project. We applied our microsatellite-based genotyping pipeline to identify 55 microsatellite loci that can distinguish between the germline of individuals diagnosed with breast cancer and healthy individuals with a sensitivity of 88.4 % and a specificity of 77.1 %. Further, we identified additional microsatellite loci that are potentially useful for distinguishing between breast cancer subtypes, revealing a possible fifth subtype. These findings are of clinical interest as possible risk diagnostics and reveal genes that may be of potential therapeutic value, including genes previously not associated with breast cancer.
AB - Genomic instability at microsatellite loci is a hallmark of many cancers, including breast cancer. However, much of the genomic variation and many of the hereditary components responsible for breast cancer remain undetected. We hypothesized that variation at microsatellites could provide additional genomic markers for breast cancer risk assessment. A total of 1,345 germline and tumor DNA samples from individuals diagnosed with breast cancer, exome sequenced as part of The Cancer Genome Atlas, were analyzed for microsatellite variation. The comparison group for our analysis, representing healthy individuals, consisted of 249 females which were exome sequenced as part of the 1,000 Genomes Project. We applied our microsatellite-based genotyping pipeline to identify 55 microsatellite loci that can distinguish between the germline of individuals diagnosed with breast cancer and healthy individuals with a sensitivity of 88.4 % and a specificity of 77.1 %. Further, we identified additional microsatellite loci that are potentially useful for distinguishing between breast cancer subtypes, revealing a possible fifth subtype. These findings are of clinical interest as possible risk diagnostics and reveal genes that may be of potential therapeutic value, including genes previously not associated with breast cancer.
KW - Breast cancer risk assessment
KW - Cancer genomics
KW - Microsatellite variation
KW - The Cancer Genome Atlas
UR - http://www.scopus.com/inward/record.url?scp=84901604759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901604759&partnerID=8YFLogxK
U2 - 10.1007/s10549-014-2908-8
DO - 10.1007/s10549-014-2908-8
M3 - Article
C2 - 24838940
AN - SCOPUS:84901604759
SN - 0167-6806
VL - 145
SP - 791
EP - 798
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -