Methods of Diagnosing or Treating Prostate Cancer Using The ERG Gene, Alone or in Combination with Other Over or Under Expressed Genes in Prostate Cancer

Abstract

The present invention relates to oncogenes or tumor suppressor genes, as well as other genes, involved in prostate cancer and their expression products, as well as derivatives and analogs thereof. Provided are therapeutic compositions and methods of detecting and treating cancer, including prostate and other related cancers. Also provided are methods of diagnosing and/or prognosing prostate cancer by determining the expression level of at least one prostate cancer-cell-specific gene, including, for example, the ERG gene or the LTF gene alone, or in combination with at least one of the AMACR gene and the DD3 gene.

1 . A method of diagnosing or prognosing prostate cancer in a subject, comprising:
 (a) measuring the expression level of an ETS-related gene (ERG) in a biological sample from the subject; and   (b) correlating the expression level of the ERG with the presence of prostate cancer in the subject or a higher predisposition of the subject to develop prostate cancer.   
     
     
         2 . The method of  claim 1 , wherein the expression level is measured by one or more methods chosen from Southern blotting, Northern blotting, and a nucleic acid amplification procedure. 
     
     
         3 . The method of  claim 1 , further comprising measuring the expression levels of the AMACR gene (SEQ ID NO:3) or the DD3 gene (SEQ ED NO:4) or both the AMACR gene and the DD3 gene, and correlating the expression levels of the ERG and the AMACR gene, the ERG and the DD3 gene or the ERG, the AMACR gene, and the DD3 gene with the presence of prostate cancer in the subject or a higher predisposition of the subject to develop prostate cancer. 
     
     
         4 . The method of  claim 1 , wherein the expression level of the ERG is detected using an oligonucleotide probe that is capable of hybridizing under high stringency conditions to SEQ ID NO:1. 
     
     
         5 . The method of  claim 1 , wherein the expression level of the ERG is detected using a nucleic acid amplification procedure and an oligonucleotide probe that is capable of hybridizing under high stringency conditions to SEQ ID NO: 1. 
     
     
         6 . The method of  claim 5 , wherein the oligonucleotide probe is capable of hybridizing under high stringency conditions comprising hybridization for 48 hours at 65° C. in 6×SSC followed by a wash in 0.1×SSX at 50° C. for 45 minutes. 
     
     
         7 . The method of  claim 6 , wherein the biological sample is chosen from a tissue sample, a blood sample, or a urine sample. 
     
     
         8 . The method of  claim 7 , wherein the biological sample is a prostate tissue sample. 
     
     
         9 . The method of  claim 7 , wherein the biological sample is the urine sample. 
     
     
         10 . The method of  claim 1 , wherein the expression level of the ERG in the biological sample is compared to the expression level of the ERG in a control sample and wherein an increased expression of the ERG in the biological sample of at least two times as compared to the expression of the ERG in the control sample indicates the presence of prostate cancer in the subject or a higher predisposition of the subject to develop prostate cancer. 
     
     
         11 . The method of  claim 10 , wherein the control sample is a noncancerous biological sample from the subject. 
     
     
         12 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the expression level of the ERG is used to indicate or predict the pathologic stage of prostate cancer. 
     
     
         21 . The method of  claim 3 , wherein the expression level of the ERG and the expression levels of the AMACR gene or the DD3 gene or both the AMACR and DD3 genes are used to indicate or predict the pathologic stage of prostate cancer. 
     
     
         22 . A method of detecting expression of an ETS-related gene ERG) in a biological sample, comprising:
 (a) combining the biological sample with at least a first and a second oligonucleotide primer under hybridizing conditions, wherein the first and the second oligonucleotide primers are capable of amplifying a target sequence of interest in SEQ ID NO: 1, wherein the biological sample is a prostate tissue sample a blood sample or a urine sample,   (b) adding at least one polymerase activity to produce a plurality of amplification products, when the target sequence is present in the biological sample,   (c) adding an oligonucleotide probe that hybridizes to at least one amplification product of the target sequence, and   (d) detecting whether a signal results from hybridization between the oligonucleotide probe and the at least one amplification product, wherein detection of the signal indicates the expression of the ERG in the biological sample.   
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 22 , further comprising detecting the expression of AMACR in the biological sample. 
     
     
         25 . The method of  claim 22 , further comprising detecting the expression of DD3 in the biological sample. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 22 , further comprising detecting the expression of AMACR and DD3 in the biological sample. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 22 , wherein the oligonucleotide probe is capable of hybridizing to SEQ ID NO: 1 or a sequence complementary thereto under high stringency conditions. 
     
     
         30 . The method of  claim 29 , wherein the oligonucleotide probe is capable of hybridizing to SEQ ID NO:1 under high stringency conditions comprising hybridization for 48 hours at 65° C. in 6×SSC followed by a wash in 0.1×SSX at 50° C. for 45 minutes. 
     
     
         31 . The method of  claim 30 , wherein the oligonucleotide probe, first oligonucleotide primer, or second oligonucleotide primer comprises a fragment of SEQ ID NO: 1 having at least 15 contiguous nucleotides of SEQ ID NO: 1 or a sequence complementary thereto. 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 22 , wherein the first oligonucleotide primer contains a sequence that hybridizes to a first sequence in the target sequence and the second oligonucleotide primer contains a sequence that hybridizes to a second sequence in a nucleic acid strand complementary to the target sequence, wherein the first sequence does not overlap with the second sequence. 
     
     
         35 . The method of  claim 25 , wherein the biological sample is urine.