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| Status |
Public on Dec 31, 2011 |
| Title |
High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multi-focal prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
Many human cancers present as multi-focal lesions. Understanding the clonal origin of multi-focal cancers is of both etiological and clinical importance. The molecular basis of multi-focal prostate cancer has previously been explored using only a limited number of isolated markers and, although independent origin is widely believed, the clonal origin of multi-focal 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 54 individual cancer and HGPIN lesions, isolated from 20 clinically localized prostate cancer cases. Identical genomic copy-number changes, shared by all same-case cancer foci, were detected in all 16 informative multi-tumor cases. In addition, both HGPIN lesions in the two multi-HGPIN cases available shared identical genomic changes. Commonly known genomic alterations, including losses at 6q15, 8p21.3-8p21.2, 10q23.2-10q23.31, 13q21.31-13q21.32, 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 multi-focal prostate cancer study, occurring 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 multi-focal cases derive from a single prostate cancer precursor clone and that this precursor may give rise to separate HGPIN foci, which through clonal expansion may progress to multi-focal invasive prostate cancer. These findings, which demonstrate the monoclonal origin of multi-focal prostate cancer, should significantly enhance our understanding of prostate carcinogenesis and potentially improve clinical management of the disease.
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| Overall design |
Copy number analysis of Affymetrix SNP 6.0 array was performed for a total of 48 cancer and HGPIN lesions from 18 prostate cancer cases. All samples have case-matched normal controls.
PL = high grade PIN from left side, PR = high grade PIN from right side, PM = high grade PIN from middle of the tissue, TL = tumour from left side, TR = tumour from right side.
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| Contributor(s) |
Boyd LK, Mao X, Xue L, Lin D, Chaplin T, Kudahetti SC, Stankiewicz E, Yu Y, Belran L, Shaw G, Hines J, Oliver RD, Berney DM, Young BD, Lu Y |
| Citation(s) |
22334418 |
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| Submission date |
May 26, 2011 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Xueying Mao |
| E-mail(s) |
x.mao@qmul.ac.uk
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| Organization name |
Queen Mary
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| Street address |
Charterhouse Square
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| City |
London |
| ZIP/Postal code |
EC1M 6BQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6801 |
[GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array |
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| Samples (66)
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| Relations |
| BioProject |
PRJNA141335 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29569_RAW.tar |
2.6 Gb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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