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| Status |
Public on Feb 01, 2013 |
| Title |
Gene copy number variations associated with patient survival in uveal melanoma |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
|
| Summary |
Analysis of DNA from fixed tissues specimens of 58 primary uveal melanomas, with known clinical outcome, to determine gene copy number variations that were associated with survival.
Abstract: Uveal melanomas can be stratified into subgroups with high or low risk of metastatic death, according to the presence of gross chromosomal abnormalities. Where a monosomy 3 uveal melanoma is detected, patient survival at three years is reduced to 50%. However, approximately 5% of patients with a disomy 3 tumour ultimately develop metastasis, and a further 5% of monosomy 3 uveal melanoma patients’ exhibit disease-free survival for more than five years. Despite extensive knowledge of the chromosomal abnormalities occurring in uveal melanoma, the genes driving metastasis are not well defined. Gene copy number variations occurring in a well-characterised cohort of 58 formalin-fixed, paraffin-embedded uveal melanoma samples were identified using the Affymetrix SNP 6.0 whole genome microarray. Four genetic sub-groups of primary uveal melanoma were represented in the patient cohort: 1) disomy 3 with long-term survival; 2) metastasizing disomy 3; 3) metastasizing monosomy 3; and 4) monosomy 3 with long-term survival. Cox regression and Kaplan-Meier survival analysis identified three genes that were associated with differences in patient survival. Patients with an amplification of CNKSR3 (6q) or RIPK1 (6p) demonstrated longer survival than those with gene deletions or no copy number change (log rank, p=0.022 and p<0.001, respectively). Conversely, those patients with an amplification of PENK (8q) showed reduced survival (log rank p<0.001). CNKSR3, RIPK1 and PENK are novel candidate metastasis regulatory genes in uveal melanoma. This is the first report of amplification of a specific gene on 6p that is associated with improved uveal melanoma patient survival and suggests that the development of uveal melanomas with a propensity to metastasise may be limited by genes on 6p.
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| Overall design |
58 samples in total. Ten disomy 3 with long-term survival. Fifteen disomy 3 with metastasising. Seventeen monosomy 3 with long-term survival. Sixteen monosomy 3 metastasising.
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| Contributor(s) |
Lake SL, Damato BE, Taktak AF, Lloyd BH, Coupland SE |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Apr 13, 2012 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Sarah Lake |
| E-mail(s) |
s.l.lake@liv.ac.uk
|
| Phone |
01517064869
|
| Fax |
01517065883
|
| URL |
http://www.loorg.org/dr-sarah-lake.html
|
| Organization name |
University of Liverpool
|
| Department |
Molecular and Clinical Cancer Medicine
|
| Lab |
Liverpool Ocular Oncology Research Group
|
| Street address |
6th Floor, Duncan Building, Daulby Street
|
| City |
Liverpool |
| ZIP/Postal code |
CH62 4US |
| 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 (58)
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| Relations |
| BioProject |
PRJNA159145 |
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