Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Chromosomal changes in primary human uveal melanomas

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Onken

PROVIDER: E-GEOD-42740 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma.

Worley Lori A LA Onken Michael D MD Person Erica E Robirds Diane D Branson Julie J Char Devron H DH Perry Arie A Harbour J William JW

Clinical cancer research : an official journal of the American Association for Cancer Research 20070301 5

<h4>Purpose</h4>To compare a gene expression-based classifier versus the standard genetic prognostic marker, monosomy 3, for predicting metastasis in uveal melanoma.<h4>Experimental design</h4>Gene expression profiling, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) were done on 67 primary uveal melanomas. Clinical and pathologic prognostic factors were also assessed. Variables were analyzed by Cox proportional hazards, Kaplan-Meier analysis, sensit ...[more]

PMID: 17332290

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Project description:Background: Germline polymorphisms can influence gene expression networks in normal mammalian tissues and can affect disease susceptibility. We and others have shown that analysis of this genetic architecture can identify single genes and whole pathways that influence complex traits including inflammation and cancer susceptibility. Whether germline variants affect gene expression in tumors which have undergone somatic alterations, and the extent to which these variants influence tumor progression, is unknown. Results: Using an integrated linkage and genomic analysis of a mouse model of skin cancer that produces both benign tumors and malignant carcinomas, we document major changes in germline control of gene expression during skin tumor development resulting from cell selection, somatic genetic events, and changes in the tumor microenvironment. The number of significant expression Quantitative Trait Loci (eQTLs) is progressively reduced in benign and malignant skin tumors when compared to normal skin. However, novel tumor-specific eQTLs are detected for several genes associated with tumor susceptibility, including Interleukin 18, Granzyme E, Sprouty homolog 2, and MAP kinase kinase 4. Conclusions: We conclude that the genetic architecture is substantially altered in tumors, and that eQTL analysis of tumors can identify host factors that influence the tumor microenvironment, MAP kinase signaling, and cancer susceptibility. A backcross was generated using male Mus spretus and female FVB/N mice; female F1 hybrids were mated with male FVB/N mice. Backcross mice (8-12 weeks old) received a single dose of DMBA (25 µg per mouse in 200 µl acetone). Starting one week after the initiation tumors were promoted with TPA (200 µl of 10-4 M solution in acetone) twice weekly for 20 weeks. Initiation and promotion were performed on doral back skin. DNA from 62 Carcinomas and matched untreated tails (used for normal DNA comparison) was obtained from tissue that was snap frozen when animals were sacrificed.

Dataset Information

Chromosomal changes in primary human uveal melanomas

Publications

Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma.

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