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Integrated analysis of expression and chromosomal organisation of genes localised on human chromosome 1q21: implications for human disease and cancer

Objective



Chromosome 1, which is the largest human chromosome and harbours about 8% of the entire human genomic information, reveals in region lq21 a most remarkable clustering of genes that fulfil important functions in development and differentiation. Among twenty-five individual genes identified and physically mapped so far, fifteen encode structural proteins that are indispensable for terminal differentiation of the human epidermis and ten are genes for S100A small calcium binding proteins involved in signal transduction and cell cycle progression.

Co-localisation of genes coding for calcium binding proteins with genes expressed late during epidermal differentiation is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Moreover, S100 proteins have been found to be differentially regulated in human cancer cells and region lq21 is often rearranged in human tumours. In addition, amplification of region lq21-q22 has recently been identified in human sarcomas.

Since the groups joining for this proposal have previously been engaged in the identification and/or mapping of these important clustered genes, it appears appropriate to concentrate European resources for a combined, multidisciplinary effort aiming at a comprehensive characterisation of all known and novel genes residing in region lq21 and their tissue-, developmental-, and differentiation specific regulation. Likewise, the potential role of these genesin genetic disorders of keratinisation that obliterate the physical and chemical resistance of human epidermis will be analyzed as will be the effects of their disproportionate representation and abnormal regulation in tumorigenesis.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Humboldt-Universität zu Berlin
Address
130,Spandauer Damm
14050 Berlin
Germany

Participants (8)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Rue Jules Hetzel 9
92190 Meudon
Centre Hospitalier Universitaire Vaudois
Switzerland
Address
29,Rue Du Bugnon
1011 Lausanne
Imperial Cancer Research Fund
United Kingdom
Address
Lincoln's Inn Fields 44
WC2A 3PX London
Institutt for Kreftforskning
Norway
Address
Montebello
0310 Oslo
Rijksuniversiteit Leiden
Netherlands
Address
55,Einsteinweg
2300 RA Leiden
The School of Pharmacy, University of London
United Kingdom
Address
29/39,Brunswick Square
WC1N 1AX London
United Medical and Dental Schools of Guy's and St Thomas's
United Kingdom
Address
St Thomas's Street London Bridge
SE1 9RT London
Universität Zürich
Switzerland
Address
75,Steinwiesstrasse
8032 Zürich