@article{272998a7607f4b8e8ec435d83f56e0dc,
title = "Integrative molecular concept modeling of prostate cancer progression",
abstract = "Despite efforts to profile prostate cancer, the genetic alterations and biological processes that correlate with the observed histological progression are unclear. Using laser-capture microdissection to isolate 101 cell populations, we have profiled prostate cancer progression from benign epithelium to metastatic disease. By analyzing expression signatures in the context of over 14,000 'molecular concepts', or sets of biologically connected genes, we generated an integrative model of progression. Molecular concepts that demarcate critical transitions in progression include protein biosynthesis, E26 transformation-specific (ETS) family transcriptional targets, androgen signaling and cell proliferation. Of note, relative to low-grade prostate cancer (Gleason pattern 3), high-grade cancer (Gleason pattern 4) shows an attenuated androgen signaling signature, similar to metastatic prostate cancer, which may reflect dedifferentiation and explain the clinical association of grade with prognosis. Taken together, these data show that analyzing gene expression signatures in the context of a compendium of molecular concepts is useful in understanding cancer biology.",
author = "Tomlins, {Scott A.} and Rohit Mehra and Rhodes, {Daniel R.} and Xuhong Cao and Lei Wang and Dhanasekaran, {Saravana M.} and Shanker Kalyana-Sundaram and Wei, {John T.} and Rubin, {Mark A.} and Pienta, {Kenneth J.} and Shah, {Rajal B.} and Chinnaiyan, {Arul M.}",
note = "Funding Information: We thank A. Menon for microarray production, B. Briggs, S. Varambally and B. Helgeson for technical assistance and R. Kuefer (University of Ulm) for tissue samples. Supported in part by Department of Defense (grants DAMD17-03-2-0033 to A.M.C. and M.A.R., PC040517 to R.M. and W81XWH-06-1-0224 to A.M.C.), the US National Institutes of Health (U54 DA021519-01A1 to A.M.C., R01 CA102872 to K.J.P and A.M.C and Prostate SPORE P50CA69568 to K.J.P., A.M.C. and R.B.S.), the Early Detection Research Network (UO1 CA111275-01 to A.M.C.) and the Cancer Center Bioinformatics Core (support grant 5P30 CA46592). K.J.P. is supported as an American Cancer Society Clinical Research Professor, D.R.R. is supported by the Cancer Biology Training Program, S.A.T. is supported by a Rackham Predoctoral Fellowship, A.M.C. is supported by a Clinical Translational Research Award from the Burroughs Welcome Foundation and S.A.T. and D.R.R. are Fellows of the Medical Scientist Training Program.",
year = "2007",
month = jan,
doi = "10.1038/ng1935",
language = "English (US)",
volume = "39",
pages = "41--51",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "1",
}