Distinguishing pca3 messenger rna species in benign and malignant prostate tissues

Abstract

This invention concerns the discovery of two distinct PCA3 mRNA sequences. One of these sequences corresponds to a short PCA3 mRNA molecule whereas the other PCA3 RNA molecule is longer as it comprises an additional sequence between exon 3 and exon 4a. The short RNA is associated with prostate cancer whereas the long RNA sequence is associated with a non-malignant state of the prostate. Based on the differential expression levels of these two PCA3 RNA sequences, protocols for the diagnosis of prostate disease are provided. The invention also relates to therapeutic approaches to prostate cancer.

1 - 23 . (canceled) 
     
     
         24 . A cDNA molecule encoding a differentially expressed prostate cancer antigen 3 (PCA3) mRNA containing an additional sequence between exon 3 and exon 4a, thereby giving rise to a long PCA3 mRNA, wherein the additional sequence interrupts the open reading frame of a PCA3 protein, thereby yielding a truncated PCA3 protein having a sequence consisting of 23 amino acids at least 90% identical to SEQ ID NO: 3. 
     
     
         25 . The cDNA molecule according to  claim 24 , wherein the molecule encodes a polypeptide having a sequence consisting of 23 amino acids at least 95% identical to SEQ ID NO: 3. 
     
     
         26 . The cDNA molecule according to  claim 24 , wherein the molecule encodes a polypeptide consisting of the complete amino acid sequence set forth in SEQ ID NO:3. 
     
     
         27 . A recombinant nucleic acid molecule comprising 5′ to 3′, a promoter effective to initiate transcription in a host cell and the cDNA molecule according to  claim 24 . 
     
     
         28 . A cell that contains the recombinant nucleic acid molecule according to  claim 27 . 
     
     
         29 . A non-human organism that contains the recombinant nucleic acid molecule according to  claim 27 . 
     
     
         30 . The cDNA molecule according to  claim 24 , comprising (i) a polynucleotide sequence at least 90% identical to a nucleotide sequence encoding a differentially expressed PCA3 polypeptide consisting of the complete amino acid sequence in SEQ ID NO:3 or (ii) the complement of the polynucleotide sequence of (i). 
     
     
         31 . A composition comprising the cDNA of  claim 24  and at least one oligonucleotide comprising a sequence complementary to at least 12 consecutive nucleotides of the cDNA of  claim 24 . 
     
     
         32 . The composition of  claim 31 , wherein the oligonucleotide is a primer. 
     
     
         33 . The composition of  claim 31 , wherein the composition comprises a pair of primers for amplifying an amplicon from the cDNA. 
     
     
         34 . The composition of  claim 33 , further comprising a labeled probe that comprises a sequence complementary to at least 12 consecutive nucleotides of the cDNA of  claim 24 . 
     
     
         35 . The composition of  claim 34 , wherein the labeled probe is a fluorescently labeled probe. 
     
     
         36 . The composition of  claim 31 , wherein the oligonucleotide is a labeled probe. 
     
     
         37 . The composition of  claim 31 , wherein the oligonucleotide is a fluorescently labeled probe. 
     
     
         38 . A composition comprising the cDNA of  claim 24  and at least one DNA polymerase. 
     
     
         39 . The composition of  claim 38 , wherein the DNA polymerase is a reverse transcriptase. 
     
     
         40 . The composition of  claim 38 , wherein the DNA polymerase is a thermostable DNA polymerase. 
     
     
         41 . The composition of  claim 38 , further comprising at least one primer.