title: Integrative analysis of genomic aberrations associated with prostate cancer progression.
abstract: Integrative analysis of genomic aberrations in the context of trancriptomic alterations will lead to a more comprehensive perspective on prostate cancer progression. Genome-wide copy number changes were monitored using array comparative genomic hybridization of laser-capture microdissected prostate cancer samples spanning stages of prostate cancer progression, including precursor lesions, clinically localized disease, and metastatic disease. A total of 62 specific cell populations from 38 patients were profiled. Minimal common regions (MCR) of alterations were defined for each sample type, and metastatic samples displayed the most number of alterations. Clinically localized prostate cancer samples with high Gleason grade resembled metastatic samples with respect to the size of altered regions and number of affected genes. A total of 9 out of 13 MCRs in the putative precursor lesion, high-grade prostatic intraepithelial neoplasia (PIN), showed an overlap with prostate cancer cases (amplifications in 3q29, 5q31.3-q32, 6q27, and 8q24.3 and deletions in 6q22.31, 16p12.2, 17q21.2, and 17q21.31), whereas postatrophic hyperplasia (PAH) did not exhibit this overlap. Interestingly, prostate cancers that do not overexpress ETS family members (i.e., gene fusion-negative prostate cancers) harbor differential aberrations in 1q23, 6q16, 6q21, 10q23, and 10q24. Integrative analysis with matched mRNA profiles identified genetic alterations in several proposed candidate genes implicated in prostate cancer progression.
authors.affiliation: Michigan Center for Translational Pathology, Department of Pathology, Department of Urology, Program of Bioinformatics, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109-0940, USA.
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yu
authors.forename: Chandan
authors.initials: C
authors.lastname: Kumar-Sinha
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.forename: Atreya
authors.initials: A
authors.lastname: Dash
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Debashis
authors.initials: D
authors.lastname: Ghosh
authors.forename: Kerby
authors.initials: K
authors.lastname: Shedden
authors.forename: James E
authors.initials: JE
authors.lastname: Montie
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D002869:Chromosome Aberrations; D002902:Chromosomes, Human, 16-18; D002906:Chromosomes, Human, 6-12 and X; D002893:Chromosomes, Human, Pair 3; D002895:Chromosomes, Human, Pair 5; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000502:physiology; D052138:Genes, Neoplasm; D015894:Genome, Human; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D046888:Tissue Array Analysis