Method of diagnosing bladder cancer

Abstract

The present invention relates to a method of diagnosing cancer in a subject comprising detecting in the DNA of said subject at least one hypermethylated CpG island associated with said cancer, wherein an elevation in the level of methylation in said CpG island of said subject, relative to the level of methylation in said CpG island of a control subject, is indicative of said CpG island being hypermethylated.

1 . A method for diagnosing non muscle-invasive bladder cancer in a subject comprising detecting in the DNA of said subject at least one hypermethylated CpG island associated with said cancer, wherein an elevation in the level of methylation in said CpG island of said subject, relative to the level of methylation in said CpG island of a control subject, is indicative of said CpG island being hypermethylated, and wherein said CpG island is selected from the group consisting of the CpG islands listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 7, Table 9, Table 10 and Table 12, wherein said method comprises detection of recurrent forms of cancer in DNA isolated from patient urine. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . A method for diagnosing non muscle-invasive bladder cancer in a subject comprising detecting in the DNA of said subject at least one hypermethylated CpG island associated with bladder cancer, wherein an elevation in the level of methylation in said CpG island of said subject, relative to the level of methylation in said CpG island of a control subject, is indicative of said CpG island being hypermethylated, wherein said method comprises detection of primary forms of cancer in DNA isolated from patient urine and wherein said at least one CpG islands methylation associated with cancer selected from the group consisting of the CpG islands listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 7, Table 9, Table 10 and Table 12, wherein said DNA is obtained from a urine sample of said subject. 
     
     
         5 - 6 . (canceled) 
     
     
         7 . A method for the prediction of the recurrence, progression or prognosis of cancer, in particular bladder cancer, comprising detecting in the DNA of said subject at least one hypermethylated CpG island associated with said cancer, wherein an elevation in the level of methylation in said CpG island of said subject, relative to the level of methylation in said CpG island of a control subject, is indicative of said CpG island being hypermethylated, and wherein said CpG island is selected from the group consisting of the CpG islands listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 7, Table 9, Table 10 and Table 12, preferably from Table 5, Table 10 and Table 12B. 
     
     
         8 . The method according to  claim 7 , whereby the CpG island is selected from the group consisting of the CpG islands in GPR103, DBCl and/or GATA2. 
     
     
         9 . The method according to  claim 1 , wherein said method comprises methylation-specific PCR (MSP). 
     
     
         10 . The method according to  claim 1 , wherein said method comprises multiplex ligation-dependent probe amplification (MLPA). 
     
     
         11 . Method of treating bladder cancer or reducing the chance of relapse of a cancer in a subject comprising at least one CpG island in the DNA of said subject which is hypermethylated in the cancer cells of said subject relative to a control subject, and wherein said hypermethylation is associated with said cancer, comprising administering to a subject in need of such treatment a therapeutically effective amount of a demethylating agent capable of selectively demethylating said at least one CpG island associated with cancer. 
     
     
         12 . The method according to  claim 11 , wherein said cancer is bladder cancer, preferably muscle invasive (MI) bladder cancer. 
     
     
         13 . The method of  claim 11 , wherein the at least one hypermethylated CpG island is selected from the group consisting of the CpG islands listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 7, Table 9, Table 10 and Table 12. 
     
     
         14 . The method of  claim 11 , wherein said treatment is part of a priming therapy for chemotherapeutic regimes. 
     
     
         15 . A pharmaceutical composition for treating aggressive bladder cancers, comprising at least one demethylating agent capable of selectively demethylating said at least one CpG island selected from the group consisting of the CpG islands listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 7, Table 9, Table 10 and Table 12, and a pharmaceutically-acceptable carrier. 
     
     
         16 . A diagnostic composition for use in a method according to  claim 1 ,  4 ,  7 , or  11  comprising a nucleic acid capable of selectively hybridizing under stringent conditions to a hypermethylated CpG islands selected from the group consisting of the CPG islands listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 7, Table 9, Table 10 and Table 12.