Chromosome 17p-linked prostrate cancer susceptibility gene and a paralog and orthologous genes

Abstract

The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human prostate cancer predisposing gene (HPC2), some alleles of which cause susceptibility to cancer, in particular prostate cancer. More specifically, the present invention relates to germline mutations in the HPC2 gene and their use in the diagnosis of predisposition to prostate cancer. The invention also relates to presymptomatic therapy of individuals who carry deleterious alleles of the HPC2 gene. The invention farther relates to somatic mutations in the HPC2 gene in human prostate cancer and their use in the diagnosis and prognosis of human prostate cancer. Additionally, the invention relates to somatic mutations in the HPC2 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the HPC2 gene, (including gene therapy, protein replacement therapy, protein mimetics, and inhibitors). The invention further relates to the screening of drugs for cancer therapy. The invention also relates to the screening of the HPC2 gene for mutations, which are useful for diagnosing the predisposition to prostate cancer. In addition, the invention relates to a paralog of human HPC2, the paralog being named ELAC1, and to orthologs of human HPC2, these being mouse Elac2, chimpanzee Elac2 and gorilla Elac2.

What is claimed is:  
     
         1 . A preparation of a polypeptide substantially free of other proteins, said polypeptide being a mutated human HPC2 polypeptide obtainable by expression of a mutated form of the nucleic acid sequence set forth in SEQ ID NO:1.  
     
     
         2 . The preparation of  claim 1  wherein a) said mutated human HPC2 polypeptide has the amino acid sequence set forth in SEQ ID NO:2 except for a mutation selected from the group consisting of i) a histidine at amino acid 781, ii) a leucine at amino acid 217, iii) a threonine at amino acid 541, and iv) a leucine at amino acid 217 and a threonine at amino acid 541 or b) said mutated human HPC2 polypeptide is obtainable by expression of a mutated form of the nucleic acid sequence set forth in SEQ ID NO:1 wherein said mutated form is an insertion of a G at base 1641.  
     
     
         3 . A preparation as claimed in  claim 1  wherein said polypeptide is labeled.  
     
     
         4 . Use of a polypeptide as defined in  claim 1  as an immunogen for antibody production.  
     
     
         5 . A use as claimed in  claim 4  wherein one or more antibodies products are subsequently labeled or bound to a solid support.