Modeling molecular development of breast cancer in canine mammary tumors.

TitleModeling molecular development of breast cancer in canine mammary tumors.
Publication TypeJournal Article
Year of Publication2020
AuthorsGraim, K, Gorenshteyn, D, Robinson, DG, Carriero, NJ, Cahill, JA, Chakrabarti, R, Goldschmidt, MH, Durham, AC, Funk, J, Storey, JD, Kristensen, VN, Theesfeld, CL, Sorenmo, KU, Troyanskaya, OG
JournalGenome Res
Date Published2020 Dec 23

<p>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 and benign and malignant tumors from each patient. We showed 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 showed 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.</p>

Alternate JournalGenome Res
PubMed ID33361113
PubMed Central IDPMC7849403
Grant ListP30 CA016520 / CA / NCI NIH HHS / United States
R01 HG006448 / HG / NHGRI NIH HHS / United States