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| Status |
Public on Feb 12, 2016 |
| Title |
Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by array
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| Summary |
Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo.
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| Overall design |
Agilent whole human genome aCGH oligonucleotide microarrays were used to assess copy number aberrations in 79 specimens from 20 patients as well as two pairs of cancer-associated fibroblasts (CAF) and benign/normal associated fibroblasts (NAF). 3 CAF/NAF sample pairs were also assessed for DNA copy number aberrations and copy-neutral LOH using the Infinium HumanOmniExpressExome BeadChip Kit.
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| Contributor(s) |
Bianchi-Frias D, Basom R, Delrow JJ, Coleman IM, Dakhova O, Qu X, Fang M, Franco OE, Ericson NG, Bielas JH, Hayward SW, True L, Morrissey C, Brown L, Bhowmick NA, Rowley D, Ittmann M, Nelson PS |
| Citation(s) |
26753621 |
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| Submission date |
Dec 31, 2015 |
| Last update date |
Feb 14, 2016 |
| Contact name |
Ilsa Coleman |
| E-mail(s) |
[email protected]
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| Phone |
206-667-1703
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| Organization name |
Fred Hutchinson Cancer Center
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| Department |
Human Biology
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| Lab |
Peter Nelson
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| Street address |
1100 Fairview Ave N, E2-112
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (2) |
| GPL16333 |
Infinium HumanOmniExpressExome BeadChip |
| GPL21289 |
Agilent-023364 Custom Whole Human Genome CGH Microarray 2x415K [Probe Name version] |
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| Samples (89)
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| Relations |
| BioProject |
PRJNA307348 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE76456_RAW.tar |
9.6 Gb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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