Novel Targets For The Diagnosis And Treatment Of Dysplasia

Abstract

An identification of patients at risk for developing cancer at early stages of disease would have a big impact on overall survival. The molecular perturbations associated with early stages of lung cancer are, however, unknown as are the gene regulatory networks forcing dysplastic cells into malignant transformation. To this end, the present invention provides an easy and efficient method for identifying diagnostic targets for the use in diagnosis or treatment monitoring of dysplasia, and the use of said targets and related substances for the diagnosis, treatment monitoring and treatment of dysplasia, in particular of low grade or high grade dysplasia related to adenocarcinoma of the lung. In particular, the invention provides a method for identifying targets for the use in diagnosis or treatment monitoring of dysplasia, in particular of low grade or high grade dysplasia related to adenocarcinoma of the lung, comprising the steps of: laser microdissection of cells from the tissue of a transgenic animal overexpressing an oncogene placed under the control of a regulatory sequence from a tissue specific gene, wherein dysplastic cells and morphologically unaltered cells are harvested, isolating RNA (1) from the dysplatic cells and isolating RNA (2) from the morphologically unaltered cells, determining, for each of the isolated RNA (1) and (2), a preferably genome wide gene expression profile, and - identifying the target as a gene being significantly overexpressed in the gene expression profile of the isolated RNA (1) in comparison with the gene expression profile of the isolated RNA (2). More particular, the invention is directed to the use of a gene identified by said method, wherein the gene is preferably selected from the group of Areg, Ereg, Adcyap1, Adora1, Afp, Apoa1, Arg2, Brunol4, Cldn2, Cldn4, Cldn8, CIu, Fst, Gpx2, Gsta4, Hnf4a, Inhbb, Lad1, Pcbd1, Pthlh, Rasgrf1, Rgs16, Stk39, Tnfsf9, preferably APOA1 or from the group of the genes Btbd11, C8orf13, Cyp1 b1, Fetub, Fut2, Klc3, Pcsk6, Pkhd1, Pla2gl1b, Psrd, Ptprn2, Rnf 128, Ros1, Sdcbp2, Sult2b1, preferably PKHD1, or of a gene product encoded thereby or of RNA or DNA sequences, which hybridize to said gene and which code for a polypeptide having the function of said gene product, or of an antibody directed against said gene product or of an antibody directed against said polypeptide, for the diagnosis or treatment monitoring of dysplasia, in particular of low grade or high grade dysplasia related to adenocarcinoma of the lung, and/or to screen for drugs against dysplasia, in particular against low grade or high grade dysplasia related to adenocarcinoma of the lung.


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