Chromosomal changes in primary human uveal melanomas [UCSF]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42739 | GEO | 2012/12/06
SECONDARY ACCESSION(S): PRJNA182984
REPOSITORIES: GEO
Similar Datasets
Project description:Uveal melanoma is the most common cancer of the eye arising from melanocytes within the choroid, ciliary bodies and iris. Almost half of uveal melanomas metastasize hematogenously to distant organs, most often the liver, where the disease becomes fatal. One of the first genetic alterations to be identified in primary uveal melanomas was monosomy 3, which was found to be strongly associated with metastasis. We used gene expression profiling to identify two phenotypically distinct classes of uveal melanomas: class 1 tumors with low-grade morphology and low metastatic risk; and class 2 tumors with aggressive morphology and high metastatic risk. Our initial studies suggested that gene expression profiling was a better predictor of metastasis than monosomy 3. For this study, BAC-array comparative genomic hybridization was used to assay genomic DNA isolated from fresh frozen primary uveal melanoma samples of known molecular class based on gene expression profiling. Independent samples were sent to the aCGH cores at the University of California, San Francisco and the Roswell Park Cancer Institute for hybridization, and log2 ratios were reported. Total genomic DNA was obtained from tumor samples that were collected at the time of treatment. Samples were analyzed by the Microarray Shared Resource at the Comprehensive Cancer Center, University of California, San Francisco or by the Microarray and Genomics Facility of the Roswell Park Cancer Institute.
2012-12-06 | E-GEOD-42739 | biostudies-arrayexpress
Project description:Uveal melanoma is the most common cancer of the eye arising from melanocytes within the choroid, ciliary bodies and iris. Almost half of uveal melanomas metastasize hematogenously to distant organs, most often the liver, where the disease becomes fatal. One of the first genetic alterations to be identified in primary uveal melanomas was monosomy 3, which was found to be strongly associated with metastasis. We used gene expression profiling to identify two phenotypically distinct classes of uveal melanomas: class 1 tumors with low-grade morphology and low metastatic risk; and class 2 tumors with aggressive morphology and high metastatic risk. Our initial studies suggested that gene expression profiling was a better predictor of metastasis than monosomy 3. For this study, BAC-array comparative genomic hybridization was used to assay genomic DNA isolated from fresh frozen primary uveal melanoma samples of known molecular class based on gene expression profiling. Independent samples were sent to the aCGH cores at the University of California, San Francisco and the Roswell Park Cancer Institute for hybridization, and log2 ratios were reported. Total genomic DNA was obtained from tumor samples that were collected at the time of treatment. Samples were analyzed by the Microarray Shared Resource at the Comprehensive Cancer Center, University of California, San Francisco or by the Microarray and Genomics Facility of the Roswell Park Cancer Institute.
2012-12-06 | E-GEOD-42738 | biostudies-arrayexpress
Project description:Uveal melanoma is the most common cancer of the eye arising from melanocytes within the choroid, ciliary bodies and iris. Almost half of uveal melanomas metastasize hematogenously to distant organs, most often the liver, where the disease becomes fatal. One of the first genetic alterations to be identified in primary uveal melanomas was monosomy 3, which was found to be strongly associated with metastasis. We used gene expression profiling to identify two phenotypically distinct classes of uveal melanomas: class 1 tumors with low-grade morphology and low metastatic risk; and class 2 tumors with aggressive morphology and high metastatic risk. Our initial studies suggested that gene expression profiling was a better predictor of metastasis than monosomy 3. For this study, BAC-array comparative genomic hybridization was used to assay genomic DNA isolated from fresh frozen primary uveal melanoma samples of known molecular class based on gene expression profiling. Independent samples were sent to the aCGH cores at the University of California, San Francisco and the Roswell Park Cancer Institute for hybridization, and log2 ratios were reported.
2012-12-06 | GSE42738 | GEO
Project description: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. 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.
2013-02-01 | E-GEOD-37259 | biostudies-arrayexpress
Project description: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.
2013-02-01 | GSE37259 | GEO
Project description:Primary uveal melanomas show multiple chromosomal aberrations. To identify genome variation in six human primary uveal melanomas, genome wide copy number variation (CNV) analyses were carried out in human primary uveal melanoma samples using array comparative genome hybridization.
2021-01-25 | GSE138404 | GEO
Project description:To predict differentially expressed miRNAs between monosomy 3 and disomy 3, and to associate these miRNAs with the clinico-pathological parameters in South Asian Indian population with uveal melanoma (UM). The study consists of six uveal melanoma primary tumour tissues of South Asian-Indian population. These six tumours have been screened for chromosome 3 aberration using Chromogenic in-situ hybridisation (CISH). Thus, sample under the study includes, three each of monosomy 3 and disomy 3. The miRNA profiling was carried out from the tumor sections of formalin-fixed paraffin embedded eyeball samples. miRNA expression profile was obtained in monosomy 3 and disomy 3 samples, analysed by unsupervised analysis (Principal Component Analysis) and supervised analysis (Significance analysis of microarray). The select up-regulated and candidate miRNAs associated with monosomy 3 uveal melanoma tumors were validated further with qRT-PCR (n=86). Thus, this study indicates the role of miRNAs in UM tumor progression and their implication in predetermining the liver metastasis. The study consists of six uveal melanoma primary tumour tissues of South Asian-Indian population. These six tumours have been screened for chromosome 3 abberation using chromogenic in-situ hybridisation (CISH). Thus, samples under the study includes three each of monosomy 3 and disomy 3. The miRNA profiling were carried out from the tumor sections of formalin-fixed paraffin embedded eyeball samples. The up-regulated miRNAs associated with monosomy 3 uveal melanoma tumors were short listed and the candidate miRNAs were validated further with qRT-PCR. Agilent one-color experiment, Organism: Homo sapiens, Agilent Human miRNA 8x15k Arrays AMADID: 021827 [Agilent miRNA labeling reagent and Hybridization Kit Cat # 5190-0408]
2015-05-14 | E-GEOD-68828 | biostudies-arrayexpress
Project description:Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression. To that end, uveal melanoma cells were studied following stable shRNA-mediated depletion of BAP1. RNA was isolated from three independent uveal melanoma cell lines each stably depleted using shRNA for either BAP1 or the control gene GFP. Two biological replicates were performed for each cell line.
2013-09-06 | E-GEOD-48863 | biostudies-arrayexpress
Project description:Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression. To that end, uveal melanoma cells were studied following stable shRNA-mediated depletion of BAP1.
2013-09-06 | GSE48863 | GEO
Project description:miRNA expression analysis was done on Uveal melanoma, metastatic and non - metastatic case in formalin fixed paraffin embedded sections, identified from case registry and confirmed by Chromosome insitu hybridization harboring monosomy 3 aberration in metastaic case and no aberration in non metastatic case. 19 miRNAs were found to be expressed only in class I tumors (choroidal melanoma) and not in class II (liver metastasis) and 11 miRNAs were found to be expressed only in class II and not in class I. The tumors were found to harbor oncomirs in both choroidal melanoma and metastasizing melanoma targeting tumor suppressor genes and metastatic suppressor genes. None of the differentially expressed miRNAs in either case were found to be located on the chromosomes which have been proved to carry chromosomal abnormalities. Rather it was found that genes targeted by the miRNAs were found to be present in chromosomal regions that are often found to be deleted 8p22, 13q and 17p.
2009-07-11 | GSE17037 | GEO