title: Clustering-Based Method for Developing a Genomic Copy Number Alteration Signature for Predicting the Metastatic Potential of Prostate Cancer.
abstract: The transition of cancer from a localized tumor to a distant metastasis is not well understood for prostate and many other cancers, partly, because of the scarcity of tumor samples, especially metastases, from cancer patients with long-term clinical follow-up. To overcome this limitation, we developed a semi-supervised clustering method using the tumor genomic DNA copy number alterations to classify each patient into inferred clinical outcome groups of metastatic potential. Our data set was comprised of 294 primary tumors and 49 metastases from 5 independent cohorts of prostate cancer patients. The alterations were modeled based on Darwin's evolutionary selection theory and the genes overlapping these altered genomic regions were used to develop a metastatic potential score for a prostate cancer primary tumor. The function of the proteins encoded by some of the predictor genes promote escape from anoikis, a pathway of apoptosis, deregulated in metastases. We evaluated the metastatic potential score with other clinical predictors available at diagnosis using a Cox proportional hazards model and show our proposed score was the only significant predictor of metastasis free survival. The metastasis gene signature and associated score could be applied directly to copy number alteration profiles from patient biopsies positive for prostate cancer.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pearlman
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Campbell
authors.affiliation: Human Genetics Program, Department of Pediatrics, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Brooks
authors.affiliation: Human Genetics Program, Department of Pediatrics, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Genshaft
authors.affiliation: Human Genetics Program, Department of Pediatrics, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Shajahan
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ittman
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: G Steven
authors.initials: GS
authors.lastname: Bova
authors.affiliation: Department of Pathology, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ilona
authors.initials: I
authors.lastname: Holcomb
authors.affiliation: NYU Cancer Institute and Department of Microbiology, NYU Langone Medical Center, New York, NY 10016, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schneider
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer