Chromosome copy number gain as a biomarker of urothelial carcinoma lethality

Abstract

Diagnostic assays for medically classifying cancer patients are provided. The method comprises assessing a tissue sample of the patient for the presence of a copy number gain of chromosome regions 1q23.3 and/or 1q21.2. Copy number gain of chromosome regions 1q23.3 and/or 1q21.2 is indicative of a less favorable prognosis as compared to the prognosis if there was no copy number gain in the same regions.

We claim: 
     
         1 - 20 . (canceled) 
     
     
         21 . A method comprising:
 (i) contacting a nucleic acid isolated from a tumor tissue sample obtained from a subject that has urothelial cell carcinoma with a detectable probe that hybridizes under stringent conditions to one or more genes selected from the group consisting of ARNT, CTSK, CTSS, ECM1, ENSA, MCL1, ANXA9, SETDB1, LASS2, ADAMTSL4, GOLPH3L, FAM63A, and HORMAD1 to form a nucleic acid-probe hybridization complex;   (ii) contacting a control nucleic acid with the detectable probe used in (i) to form a control nucleic acid-probe hybridization complex; and   (iii) measuring the level of formation of the nucleic acid-probe hybridization complex and the level of formation of the control nucleic acid-probe hybridization complex, wherein a copy number gain in the one or more genes exists when the level of formation of the nucleic acid-probe hybridization complex is higher than the level of formation of the control nucleic acid-probe hybridization complex, and   wherein the control nucleic acid does not have a copy number gain in the one or more genes.   
     
     
         22 . The method of  claim 21 , further comprising extracting nucleic acid from the tumor tissue sample prior to performing the hybridization-based assay. 
     
     
         23 . The method of  claim 21 , wherein the detectable probe is a DNA probe. 
     
     
         24 . The method of  claim 23 , wherein the DNA probe is fluorescently labeled. 
     
     
         25 . The method of  claim 21 , wherein the tumor tissue sample is obtained from a human subject that is known to have invasive or metastatic urothelial carcinoma. 
     
     
         26 . The method of  claim 21 , wherein the isolated nucleic acid is mRNA. 
     
     
         27 . The method of  claim 21 , wherein the isolated nucleic acid is genomic DNA. 
     
     
         28 . The method of  claim 21 , further comprising, prior to step (i), obtaining the tumor tissue sample from the subject that has urothelial carcinoma. 
     
     
         29 . A method comprising:
 (i) contacting a nucleic acid isolated from a tumor sample obtained from a subject that has urothelial cell carcinoma with a pair of oligonucleotide primers under conditions to specifically amplify one or more genes selected from the group consisting of ARNT, CTSK, CTSS, ECM1, ENSA, MCL1, ANXA9, SETDB1, LASS2, ADAMTSL4, GOLPH3L, FAM63A, and HORMAD1 to produce an amplification product;   (ii) contacting a control nucleic acid with the pair of oligonucleotide primers and under the conditions in (i) to produce a control amplification product; and   (iii) measuring the amount of the amplification product in the tumor sample and the amount of the control amplification product,   wherein a copy number gain in the one or more genes exists when the amount of the amplification product in the tumor sample is higher than the amount of the control amplification product, and   wherein the control sample does not have a copy number gain in the one or more genes.   
     
     
         30 . The method of  claim 29 , wherein the nucleic acid is mRNA. 
     
     
         31 . The method of  claim 29 , wherein the nucleic acid is genomic DNA. 
     
     
         32 . The method of  claim 29 , further comprising, prior to step (i), obtaining the tumor tissue sample from the subject that has urothelial carcinoma. 
     
     
         33 . The method of  claim 29 , further comprising extracting nucleic acid from the tumor tissue sample prior to performing the quantitative amplification-based assay. 
     
     
         34 . The method of  claim 29 , wherein the tumor tissue sample is obtained from a human subject that is known to have invasive or metastatic urothelial carcinoma.