title: High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multifocal prostate cancer.
abstract: Many human cancers present as multifocal lesions. Understanding the clonal origin of multifocal cancers is of both etiological and clinical importance. The molecular basis of multifocal prostate cancer has previously been explored using a limited number of isolated markers and, although independent origin is widely believed, the clonal origin of multifocal prostate cancer is still debatable. We attempted to address clonal origin using a genome-wide copy-number analysis of individual cancer and high-grade prostatic intraepithelial neoplasia (HGPIN) lesions. Using Affymetrix array 6.0 copy-number analysis, we compared the genomic changes detected in 48 individual cancer and HGPIN lesions, isolated from 18 clinically localized prostate cancer cases. Identical genomic copy-number changes, shared by all same-case cancer foci, were detected in all 13 informative cases displaying multiple tumor foci. In addition, individual HGPIN lesions in the two multifocal-HGPIN cases available shared identical genomic changes. Commonly known genomic alterations, including losses at 6q15, 8p21.3-8p21.2, 10q23.2-10q23.31, 16q22.3, 16q23.2-16q23.3 and 21q22.2-21q22.3 regions and gain of 8q24.3 were the most frequently detected changes in this study and each was detected in all same-case foci in at least one case. Microarray data were confirmed by fluorescence in situ hybridization in selected foci. Our high-resolution genome-wide copy-number data suggest that many multifocal cases derive from a single prostate cancer precursor clone and that this precursor may give rise to separate HGPIN foci and may further progress to multifocal invasive prostate cancer. These findings, which demonstrate the monoclonal origin of multifocal prostate cancer, should significantly enhance our understanding of prostate carcinogenesis.
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Lara K
authors.initials: LK
authors.lastname: Boyd
authors.forename: Xueying
authors.initials: X
authors.lastname: Mao
authors.forename: Liyan
authors.initials: L
authors.lastname: Xue
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lin
authors.forename: Tracy
authors.initials: T
authors.lastname: Chaplin
authors.forename: Sakunthala C
authors.initials: SC
authors.lastname: Kudahetti
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stankiewicz
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Yu
authors.forename: Luis
authors.initials: L
authors.lastname: Beltran
authors.forename: Greg
authors.initials: G
authors.lastname: Shaw
authors.forename: John
authors.initials: J
authors.lastname: Hines
authors.forename: R Tim D
authors.initials: RT
authors.lastname: Oliver
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
mesh_terms: D000368:Aged; D060965:Clonal Evolution; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009385:Neoplastic Processes; D020411:Oligonucleotide Array Sequence Analysis; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results