Recurrent gene fusions in prostate cancer

1. An in vitro method for detecting a gene fusion in a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof, the method comprising:

(a) forming a hybridized structure comprising:

i) a nucleic acid comprising a gene fusion, wherein said gene fusion comprises a 5′ portion fused to a 3′ portion at a fusion junction and said gene fusion is selected from the group consisting of:

(1) a transmembrane protease, serine 2 (TMPRSS2):ETV5 gene fusion wherein the 5′ portion of the gene fusion comprises exon 1 of TMPRSS2 and the 3′ portion of the gene fusion comprises exon 2 of ETVS5;

(2) a solute carrier family 45, member 3 (SLC45A3):ETV5 gene fusion wherein the 5′ portion of the gene fusion comprises exon 1 of SLC45A3 and the 3′ portion of the gene fusion comprises exon 8 of ETV5;

(3) a SLC45A3:ETV1 gene fusion wherein the 5′ portion comprises exon 1 of SLC45A3 and the 3′ portion of the gene fusion comprises exon 5 of ETV1;

(4) a HERV-K_22q11.23:ETV1 gene fusion wherein the 5′ portion comprises nucleotides 1-362 of SEQ ID NO:421 and the 3′ portion comprises exon 5 of ETV1; and

(5) a C15ORF21:ETV1 gene fusion wherein the 5′ portion comprises exons 1-2 of C15ORF21 and the 3′ portion of the gene fusion comprises exon 6 of ETV1; and

ii) a detectably labeled probe specifically hybridized to said nucleic acid and spanning said fusion junction; and

(b) detecting the gene fusion in the human biological sample by detecting said hybridized structure in said biological sample.

2. The method of claim 1 , wherein the 5′ portion of the gene fusion further comprises a promoter region.

3. The method of claim 1 , wherein the nucleic acid comprising the gene fusion is a genomic DNA.

4. The method of claim 1 , wherein the nucleic acid comprising the gene fusion is a chimeric mRNA.

5. The method of claim 1 , wherein the human biological sample is a sample selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions, and prostate cells.

6. The method of claim 1 , wherein detecting said hybridized structure comprises using a technique selected from the group consisting of in situ hybridization (ISH), microarray, Southern blot, and northern blot.

7. The method of claim 1 , wherein the nucleic acid comprising the gene fusion is produced using an amplification technique selected from the group consisting of polymerase chain reaction, reverse transcription polymerase chain reaction, transcription-mediated amplification, ligase chain reaction, strand displacement amplification, and nucleic acid sequence based amplification.

8. An in vitro method for detecting a gene fusion in a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof, the method comprising:

(a) forming a hybridized structure comprising:

i) a nucleic acid comprising a gene fusion, wherein said gene fusion comprises a 5′ portion fused to a 3′ portion at a fusion junction, and said gene fusion is selected from the group consisting of:

(1) a TMPRSS2:ETV5 gene fusion wherein the 5′ portion of the gene fusion comprises exon 1 of TMPRSS2 and the 3′ portion of the gene fusion comprises exon 2 of ETV5;

(2) a SLC45A3:ETV5 gene fusion wherein the 5′ portion of the gene fusion comprises exon 1 of SLC45A3 and the 3′ portion of the gene fusion comprises exon 8 of ETVS5;

(3) a SLC45A3:ETV1 gene fusion wherein the 5′ portion comprises exon 1 of SLC45A3 and the 3′ portion of the gene fusion comprises exon 5 of ETV1;

(4) a HERV-K_22q11.23:ETV1 gene fusion wherein the 5′ portion comprises nucleotides 1-362 of SEQ ID NO:421 and the 3′ portion comprises exon 5 of ETV1; and

(5) a C15ORF21:ETV1 gene fusion wherein the 5′ portion comprises exons 1-2 of C15ORF21 and the 3′ portion of the gene fusion comprises exon 6 of ETV1; and

ii) a first detectably labeled probe specifically hybridized to the 5′ portion of the gene fusion and a second detectably labeled probe specifically hybridized to the 3′ portion of the gene fusion; and

(b) detecting the gene fusion in the human biological sample by detecting said hybridized structure in said biological sample.

9. The method of claim 8 , wherein the 5′ portion of the gene fusion further comprises a promoter region.

10. The method of claim 8 , wherein the nucleic acid comprising the gene fusion is a genomic DNA.

11. The method of claim 8 , wherein the nucleic acid comprising the gene fusion is a chimeric mRNA.

12. The method of claim 8 , wherein the human biological sample is a sample selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions, and prostate cells.

13. The method of claim 8 , wherein detecting said hybridized structure comprises using in situ hybridization (ISH).

14. The method of claim 8 , wherein the nucleic acid comprising the gene fusion is produced using an amplification technique selected from the group consisting of polymerase chain reaction, reverse transcription polymerase chain reaction, transcription-mediated amplification, ligase chain reaction, strand displacement amplification, and nucleic acid sequence based amplification.

15. The method of claim 1 , wherein the nucleic acid comprising the gene fusion is produced using a first amplification oligonucleotide that is complementary to the 5′ portion of the gene fusion and a second amplification oligonucleotide that is complementary to the 3′ portion of the gene fusion.

16. The method of claim 8 , wherein the nucleic acid comprising the gene fusion is produced using a first amplification oligonucleotide that is complementary to the 5′ portion of the gene fusion and a second amplification oligonucleotide that is complementary to the 3′ portion of the gene fusion.

17. An in vitro method for detecting a gene fusion in a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof, the method comprising:

(a) forming a hybridized structure comprising:

i) a nucleic acid comprising a gene fusion, wherein said gene fusion comprises a 5′ portion fused to a 3′ portion at a fusion junction and said gene fusion is selected from the group consisting of:

(1) a TMPRSS2:ETV5 gene fusion wherein the 5′ portion of the gene fusion comprises exon 1 of TMPRSS2 and the 3′ portion of the gene fusion comprises exon 2 of ETV5;

(2) a SLC45A3:ETV5 gene fusion wherein the 5′ portion of the gene fusion comprises exon 1 of SLC45A3 and the 3′ portion of the gene fusion comprises exon 8 of ETV5;

(3) a SLC45A3:ETV1gene fusion wherein the 5′ portion comprises exon 1 of SLC45A3 and the 3′ portion of the gene fusion comprises exon 5 of ETV1;

(4) a HERV-K_22q11.23:ETV1 gene fusion wherein the 5′ portion comprises nucleotides 1-362 of SEQ ID NO:421 and the 3′ portion comprises exon 5 of ETV1; and

(5) a C15ORF21:ETV1 gene fusion wherein the 5′ portion comprises exons 1-2 of C15ORF21 and the 3′ portion of the gene fusion comprises exon 6 of ETV1; and

ii) a first amplification primer specifically hybridized to said 5′ component and a second amplification primer specifically hybridized to said 3′ component;

(b) amplifying a portion of the nucleic acid using a nucleic acid amplification reaction to produce an amplicon; and

(c) detecting the gene fusion in the human biological sample by detecting in vitro the amplicon.

18. The method of claim 17 wherein detecting the amplicon comprises hybridizing a directly labeled probe to the amplicon or use of an intercalating dye.

19. The method of claim 17 wherein the 5′ portion of the gene fusion further comprises a promoter region.

20. The method of claim 17 , wherein the nucleic acid comprising the gene fusion is a genomic DNA.

21. The method of claim 17 , wherein the nucleic acid comprising the gene fusion is a chimeric mRNA.

22. The method of claim 17 , wherein the human biological sample is a sample selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions, and prostate cells.

23. The method of claim 17 , wherein the amplification reaction is selected from the group consisting of polymerase chain reaction, reverse transcription polymerase chain reaction, transcription-mediated amplification, ligase chain reaction, strand displacement amplification, and nucleic acid sequence based amplification.