Prostate cancer-specific alternations in ERG gene expression and detection and treatment methods based on those alterations

A method of detecting an increased probability that a biological sample contains prostate cancer, the method comprising:

• (a) combining the biological sample with at least a first and a second oligonucleotide primer under hybridizing conditions, wherein the biological sample comprises nucleic acid isolated from human prostate epithelial cells and does not contain nucleic acid isolated from human prostate endothelial cells, and wherein the first and the second oligonucleotide primer are capable of amplifying (1) an EPC1target sequence that selectively hybridizes to EPC1 (SEQ ID NO:3) but does not hybridize to ERG1, ERG2, ERG3, ERG4, ERG5, ERG6, ERG7, ERG8, ERG9, or EPC2 (SEQ ID NO:5) under high stringency hybridization conditions, or (2), an EPC2 target sequence that selectively hybridizes to EPC2 (SEQ ID NO:5) but does not hybridize to ERG1, ERG2, ERG3, ERG4, ERG5, ERG6, ERG7, ERG8, ERG9, or EPC1 (SEQ ID NO:3) under high stringency hybridization, conditions, wherein the EPC1 target sequence comprises all or part of nucleotides 788 to 1019 of SEQ ID NO:3 or the EPC2 target sequence comprises all or part of nucleotides 127 to 807 of SEQ ID NO:5;
• (b) amplifying a plurality of amplification products when the EPC1 or EPC2 target sequence is present in the biological sample by adding at least one polymerase activity to the biological sample containing the first and second oligonucleotide primers;
• (c) immobilizing the plurality of amplification products;
• (d) combining an oligonucleotide probe with the immobilized plurality of amplification products to thereby permit the probe to hybridize to at least one immobilized amplification product;
• (e) detecting whether a signal results from hybridization between the oligonucleotide probe and at least one amplification product;
• and
• (f) correlating the detection of the signal with the expression of EPC1 or EPC2 in human prostate epithelial cells and the increased probability that the biological sample contains prostate cancer.

A method of detecting the expression of Ets Related Gene 8(ERG8), ERG Prostate Cancer-specific isoform 1 (EPC1), or ERG Prostate Cancer-specific isoform 2 (EPC2) in a nucleic acid sample isolated from human prostate epithelial cells, the method comprising:

• (a) combining the nucleic acid sample isolated from human prostate epithelial cells with at least a first and a second oligonucleotide primer under hybridizing conditions, wherein the first and the second oligonucleotide primer are capable of amplifying (1) an ERG8 target sequence that selectively hybridizes to the ERG8 isoform but does not hybridize to Ets Related Gene 1 (ERG1), Ets Related Gene 2 (ERG2), Ets Related Gene 3 (ERG3), Ets Related Gene 4 (ERG4), Ets Related Gene 5 (ERG8), Ets Related Gene 6 (ERG6), Ets Related Gene 7 (ERG7), Ets Related Gene 9 (ERG9), EPC1 (SEQ ID NO:3), or EPC2 (SEQ ID NO:5) under high stringency hybridization conditions, (2) an EPC1 target sequence that selectively hybridizes to EPC1 (SEQ ID NO:3) but does not hybridize to ERG1, ERG2, ERG3, ERG4, ERG5, ERG6, ERG7, ERG8, ERG9, or EPC2 (SEQ ID NO:5) under high stringency hybridization conditions, or (3) an EPC2 target sequence that selectively hybridizes to EPC2 (SEQ ID NO:5) but does not hybridize to ERG1, ERG2, ERG3, ERG4, ERG5, ERG6, ERG7, ERG8, ERG9, or EPC1 (SEQ ID NO:3) under high stringency hybridization conditions, wherein the ERG8 target sequence comprises all or part of nucleotides 803 to 1168 of SEQ ID NO:
• 1, the EPC1 target sequence comprises all or part of nucleotides 788 to 1019 of SEQ ID NO:3, or the EPC2 target sequence comprises all or part of nucleotides 127 to 807 of SEQ ID NO:5;
• (b) anaplifying a plurality of amplification products when the ERG8, EPC1, or EPC2 target sequence is present in the nucleic acid sample by adding at least one polymerase activity to the biological sample containing the first and second oligonucleotide primers;
• (c) immobilizing the plurality of amplification products;
• (d) combining an oligonucleotide probe with the immobilized plurality of amplification products to thereby pea mit the probe to hybridize to at least one immobilized amplification product;
• and
• (e) detecting whether a signal results from hybridization between the oligonucleotide probe and at least one amplification product.