RT Journal
A1 Graim, Kiley
A1 Gorenshteyn, Dmitriy
A1 Robinson, David G
A1 Carriero, Nicholas J
A1 Cahill, James Andrew
A1 Chakrabarti, Rumela
A1 Goldschmidt, Michael H
A1 Durham, Amy C
A1 Funk, Julien
A1 Storey, John
A1 Kristensen, Vessela N
A1 Theesfeld, Chandra L
A1 Sorenmo, Karin U
A1 Troyanskaya, Olga G.
T1 Modeling molecular development of breast cancer in canine mammary tumors
JF Genome Research 
JO Genome Research 
YR 2020 
FD December 23 
DO 10.1101/gr.256388.119 
SP gr.256388.119 
UL http://genome.cshlp.org/content/early/2020/12/23/gr.256388.119.abstract 
AB Understanding the changes in diverse molecular pathways underlying the development of breast tumors is critical for improving diagnosis, treatment, and drug development. Here, we used RNA-profiling of canine mammary tumors (CMTs) coupled with a robust analysis framework to model molecular changes in human breast cancer. Our study leveraged a key advantage of the canine model, the frequent presence of multiple naturally occurring tumors at diagnosis, thus providing samples spanning normal tissue, benign and malignant tumors from each patient. We demonstrated human breast cancer signals, at both expression and mutation level, are evident in CMTs. Profiling multiple tumors per patient enabled by the CMT model allowed us to resolve statistically robust transcription patterns and biological pathways specific to malignant tumors versus those arising in benign tumors or shared with normal tissues. We demonstrated that multiple-histological-samples per patient is necessary to effectively capture these progression-related signatures, and that carcinoma-specific signatures are predictive of survival for human breast cancer patients. To catalyze and support similar analyses and use of the CMT model by other biomedical researchers, we provide FREYA, a robust data processing pipeline and statistical analyses framework.