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Human Melanoma: From Transcriptome to Tumor Biology.

English title Human Melanoma: From Transcriptome to Tumor Biology.
Applicant Dummer Reinhard
Number 103671
Funding scheme Project funding
Research institution Dermatologische Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Experimental Cancer Research
Start/End 01.06.2004 - 31.03.2008
Approved amount 200'592.00
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All Disciplines (2)

Discipline
Experimental Cancer Research
Dermatology

Keywords (5)

melanoma; microarray; transcriptoma; molecular biology; tissue array

Lay Summary (English)

Lead
Lay summary
The development of cancer is a complex and evolving process which involves genetic changes and interactions with the stroma and immune system of the host. These result in profound alterations of cellular functions affecting apoptosis, proliferation, migration and immune surveillance. Cutaneous melanoma is an often fatal neoplasm derived from melanocytes and it accounts for most skin cancer deaths. In early stages of the disease a neoplasm may be cured by surgery. In advanced stages however, therapeutic intervention usually fails to improve survival despite advances in immunotherapy. A detailed investigation of the disturbances in gene regulation promises to identify new molecular targets for therapy, more specific prognostic markers and explain melanomas molecular course.
The complexity of cellular metabolism and the dozens of multiply interconnected regulatory pathways have until recently prohibited the formulation of a unifying overview of melanoma. Gene expression profiling allows for simultaneous analysis of the entire genome which offers the strongest likelyhood for a detailed molecular understanding.
Using expression profiling in conjunction with clinical information on the primary tumor, therapy and outcome for the patient, and bioptic material for immunohistochemistry, the project will address the multifactorial changes in human melanoma. We have already investigated short time melanoma cultures that have been shown to represent the original tumor lesion from the context of HLA (human major histocompatibility complex) and H-CAR (human coxsackie- and adenovirus receptor) expression. We will continue to perform intra-individual and inter-individual comparisons of gene expression patterns, using human melanocytes as the basic control.
We have the opportunity to investigate many melanoma cell cultures including multiple samples derived from single individuals from various anatomical sites and from different tumor stages (including primarytumors) against the background context of detailed clinical information.The following investigations are proposed:

1)Detection of differential transcription by microarray hybridizationtechnique in order to identify possible characteristic expression profiles in cell cultures from various stages from individuals with known clinical history and disease outcome.
2)Confirmation of transcription levels and activity of key factors byRT-PCR (light cycler), FACS-analyses, western blotting, cell culture experiments and by immunohistochemical examination of the original samples prepared on tissue arrays.
3)If necessary, several tumors can be used to establish tumors in nudemice as a model for specific therapeutic targeting.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
63704 Longitudinal analysis of immune escape and gene expression pro- files in human melanoma 01.06.2001 Project funding

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