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| Status |
Public on May 18, 2016 |
| Title |
Copy number variation analysis of hepatic metastases from uveal melanoma |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
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| Summary |
Metastatic uveal melanoma (MUM) is chemoresistant and usually fatal within one year of diagnosis. There is an urgent need to better understand disease pathogenesis, in order to determine key drivers of the metastatic process that could be effectively targeted by therapy. Gene copy number variations occurring in a rare cohort of 13 metastatic and six matched primary, formalin-fixed, paraffin-embedded uveal melanoma samples were identified using the Affymetrix Genome-Wide Human SNP 6.0 Array. Gross chromosomal abnormalities commonly seen in primary UM and associated with the development of metastasis were observed in the MUMs. The most common CNVs were gene amplifications on chromosome 8q, especially in the region 8q24.3. Interestingly, deletions on chromosome 3 were detected at a lower frequency. Genomic profiles of PUM-MUM pairs varied in their degree of similarity and complexity. No genes were altered being unique to either all PUMs or all MUMs of the pairs, but 135 gene CNVs were consistently shared. Of these genes, 125 were amplifications located on chr. 8q24.3. Five genes in the region 8q24.3 and two genes on chromosome 3 were selected for validation by immunohistochemistry because of their known function in cancer (BCL6, C-MYC, E2F5, PTP4A3, SNAI2, and WISP1), or known importance in UM pathology (BAP1). The functional effect of these CNVs on protein expression was confirmed; amplified genes showed increased expression and deleted genes reduced expression. To conclude, our data demonstrate frequent amplification of chromosome 8q in MUMs, suggesting that genes facilitating the expansion of UM in the metastatic niche occur in this region. Furthermore, validation of a range of amplified 8q genes at the protein level strongly indicates the CNVs may be functional and, contribute to MUM biology.
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| Overall design |
19 samples in total: 13 metastatic uveal melanoma (MUMs) and in six cases their paired primary UM (PUMs)
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| Contributor(s) |
McCarthy C, Kalirai H, Lake SL, Dodson A, Damato BE, Coupland SE |
| Citation(s) |
26523470 |
| Submission date |
Jun 05, 2015 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Sarah E Coupland |
| E-mail(s) |
s.e.coupland@liverpool.ac.uk
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| Organization name |
University of Liverpool
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| Department |
Molecular and Clinical Cancer Medicine
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| Lab |
Liverpool Ocular Oncology Research Group
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| Street address |
6th Floor Duncan Building, Daulby Street
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| City |
Liverpool |
| ZIP/Postal code |
L69 3GA |
| 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 (19)
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| GSM1704744 |
Metastatic Uveal Melanoma, sample07 |
| GSM1704745 |
Metastatic Uveal Melanoma, sample08 |
| GSM1704746 |
Metastatic Uveal Melanoma, sample09 |
| GSM1704747 |
Metastatic Uveal Melanoma, sample10 |
| GSM1704748 |
Metastatic Uveal Melanoma, sample11 |
| GSM1704749 |
Metastatic Uveal Melanoma, sample12 |
| GSM1704750 |
Metastatic Uveal Melanoma, sample13 |
| GSM1704751 |
Metastatic Uveal Melanoma, sample17 |
| GSM1704752 |
Metastatic Uveal Melanoma, sample18 |
| GSM1704753 |
Metastatic Uveal Melanoma, sample21 |
| GSM1704754 |
Primary Uveal Melanoma, sample02 |
| GSM1704755 |
Primary Uveal Melanoma, sample04 |
| GSM1704756 |
Primary Uveal Melanoma, sample05 |
| GSM1704757 |
Primary Uveal Melanoma, sample08 |
| GSM1704758 |
Primary Uveal Melanoma, sample09 |
| GSM1704759 |
Primary Uveal Melanoma, sample18 |
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| Relations |
| BioProject |
PRJNA285989 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69614_RAW.tar |
733.1 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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