Recurrent gene fusions in prostate cancer

• US 9,957,569 B2
• Filed: 11/18/2008
• Issued: 05/01/2018
• Est. Priority Date: 09/12/2005
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Chinnaiyan, Arul M., Han, Bo, Kumar, Chandan
• Primary Examiner(s): Salmon, Katherine D
• Application Number:
  US12/272,865
• Publication Number:
  US 20090239221A1
• Time in Patent Office: 3,451 Days
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

Recurrent gene fusions in prostate cancer of androgen regulated genes or housekeeping genes and ETS family member genes are described. Compositions and methods having utility in prostate cancer diagnosis, research, and therapy are also provided.

Claims

1. A method for detecting a solute carrier family 45, member 3:

ETS-related-gene (SLC45A3;

ERG) gene fusion in a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof, the method comprising;

(a) contacting a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof with a detectably labeled probe specific for a SLC45A3;

ERG gene fusion; and

(b) detecting the SLC45A3;

ERG gene fusion by detecting a hybridized structure comprising;

i) a nucleic acid comprising a SLC45A3;

ERG gene fusion having a 5′

portion joined at a fusion junction to a 3′

portion, said 5′

portion of the gene fusion comprising 8 consecutive nucleotides from chromosome 1 at locus 1q32 and said 3′

portion comprising 8 consecutive nucleotides from chromosome 21 at locus 21q22; and

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

2. The method of claim 1, wherein the human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, or semen.

3. The method of claim 1, wherein:

a) said 5′

portion is complementary to probe RP11-1089F13 or probe RP11-131E5;

b) said 3′

portion is complementary to probe RP11-24A11 or probe RP11-476D 17;

c) said 5′

portion comprises a sequence that is SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

that is a fragment of SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

that is complementary to SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

or that is complementary to a fragment of SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

or

d) said 3′

portion comprises a sequence that is SEQ ID NO;

432 or SEQ ID NO;

433;

that is a fragment of SEQ ID NO;

432 or SEQ ID NO;

433;

that is complementary to SEQ ID NO;

432 or SEQ ID NO;

433;

or that is complementary to a fragment of SEQ ID NO;

432 or SEQ ID NO;

433.

4. The method of claim 1 wherein said nucleic acid is the product of an amplification reaction or is a SLC45A3:

ERG chimeric mRNA transcript.

5. The method of claim 1 wherein the 5′

portion of the SLC45A3;

ERG gene fusion comprises the 5′

untranslated region portion of SLC45A3.

6. The method of claim 1 wherein the 5′

portion of the SLC45A3;

ERG gene fusion comprises a nucleotide sequence comprising an androgen response element that interacts specifically with an androgen or an androgen signaling molecule.

7. The method of claim 1 wherein said 5′

portion of the gene fusion comprises 8 consecutive nucleotides from chromosome 1 at locus 1q32.1 and said 3′

portion of the gene fusion comprises 8 consecutive nucleotides from chromosome 21 at locus 21q22.13-21q22.2.

8. The method of claim 1 wherein the detectably labeled probe specific for said SLC45A3:

ERG gene fusion is directly labeled with a detectable label.

9. A method for detecting a solute carrier family 45, member 3:

ETS-related-gene (SLC45A3;

ERG) gene fusion in a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof, the method comprising;

(a) contacting a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof with a first detectably labeled probe and a second detectably labeled probe; and

(b) detecting the SLC45A3;

ERG gene fusion by detecting a hybridized structure comprising;

i) a nucleic acid comprising a SLC45A3;

ERG gene fusion, said SLC45A3;

ERG gene fusion having a 5′

portion fused to a 3′

portion, said 5′

portion of the gene fusion comprising 8 consecutive nucleotides from chromosome 1 at locus 1q32 and said 3′

portion comprising 8 consecutive nucleotides from chromosome 21 at locus 21q22;

ii) said first detectably labeled probe specifically hybridized to said 5′

portion of the SLC45A3;

ERG gene fusion; and

ii) said second detectably labeled probe specifically hybridized to said 3′

portion of the SLC45A3;

ERG gene fusion.

10. The method of claim 9 wherein detecting said hybridized structure comprises detecting colocalization of the first and second probes by a fluorescence in situ hybridization method.

11. The method of claim 9, wherein the human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, or semen.

12. The method of claim 9, wherein:

a) said 5′

portion is complementary to probe RP11-1089F13 or probe RP11-131E5;

b) said 3′

portion is complementary to probe RP11-24A11 or probe RP11-476D 17;

c) said 5′

portion comprises a sequence that is SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

that is a fragment of SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

that is complementary to SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

or that is complementary to a fragment of SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

or

d) said 3′

portion comprises a sequence that is SEQ ID NO;

432 or SEQ ID NO;

433;

that is a fragment of SEQ ID NO;

432 or SEQ ID NO;

433;

that is complementary to SEQ ID NO;

432 or SEQ ID NO;

433;

or that is complementary to a fragment of SEQ ID NO;

432 or SEQ ID NO;

433.

13. The method of claim 9, wherein the 5′

portion of the SLC45A3;

ERG gene fusion comprises the 5′

untranslated region portion of SLC45A3.

14. The method of claim 9 wherein the 5′

portion of the SLC45A3;

ERG gene fusion comprises a nucleotide sequence comprising an androgen response element that interacts specifically with an androgen or an androgen signaling molecule.

15. The method of claim 9 wherein said 5′

portion of the gene fusion comprises 8 consecutive nucleotides from chromosome 1 at locus 1q32.1 and said 3′

portion of the gene fusion comprises 8 consecutive nucleotides from chromosome 21 at locus 21q22.13-21q22.2.

16. The method of claim 9 wherein said first probe is directly labeled with a first detectable label and said second probe is directly labeled with a second detectable label.

17. A method for detecting a solute carrier family 45, member 3:

ETS-related-gene (SLC45A3;

ERG) gene fusion in a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof, the method comprising;

(a) contacting a human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof with a first oligonucleotide primer and a second oligonucleotide primer;

(b) hybridizing the first and second oligonucleotide primers to a nucleic acid comprising a SLC45A3;

ERG gene fusion, said SLC45A3;

ERG gene fusion having a 5′

portion joined at a fusion junction to a 3′

portion, said 5′

portion of the gene fusion comprising 8 consecutive nucleotides from chromosome 1 at locus 1q32 and said 3′

portion comprising 8 consecutive nucleotides from chromosome 21 at locus 21q22;

(c) amplifying a portion of the nucleic acid comprising said SLC45A3;

ERG gene fusion using a nucleic acid amplification reaction to produce a SLC45A3;

ERG gene fusion nucleic acid amplification product comprising said fusion junction; and

(d) detecting the SLC45A3;

ERG gene fusion by detecting the SLC45A3;

ERG gene fusion nucleic acid amplification product comprising said fusion junction,

wherein the first oligonucleotide primer is complementary to the 5′

portion of the SLC45A3;

ERG gene fusion and the second oligonucleotide primer is complementary to the 3′

portion of the SLC45A3;

ERG gene fusion.

18. The method of claim 17, wherein the human biological sample comprising prostate tissue, prostate cells, prostate secretions, or fractions thereof is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, or semen.

19. The method of claim 17, wherein:

a) said 5′

portion is complementary to probe RP11-1089F13 or probe RP11-131E5;

b) said 3′

portion is complementary to probe RP11-24A11 or probe RP11-476D 17;

c) said 5′

portion comprises a sequence that is SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

that is a fragment of SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

that is complementary to SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

or that is complementary to a fragment of SEQ ID NO;

320, SEQ ID NO;

334, or SEQ ID NO;

335;

or

d) said 3′

portion comprises a sequence that is SEQ ID NO;

432 or SEQ ID NO;

433;

that is a fragment of SEQ ID NO;

432 or SEQ ID NO;

433;

that is complementary to SEQ ID NO;

432 or SEQ ID NO;

433;

or that is complementary to a fragment of SEQ ID NO;

432 or SEQ ID NO;

433.

20. The method of claim 17 wherein the 5′

portion of the SLC45A3;

ERG gene fusion comprises the 5′

untranslated region portion of SLC45A3.

21. The method of claim 17 wherein the 5′

portion of the SLC45A3;

ERG gene fusion comprises a nucleotide sequence comprising an androgen response element that interacts specifically with an androgen or an androgen signaling molecule.

22. The method of claim 17 wherein said 5′

portion of the gene fusion comprises 8 consecutive nucleotides from chromosome 1 at locus 1q32.1 and said 3′

portion of the gene fusion comprises 8 consecutive nucleotides from chromosome 21 at locus 21q22.13-21q22.2.

23. The method of claim 17 wherein detecting the SLC45A3:

ERG gene fusion nucleic acid amplification product comprises use of a real-time amplification method or a labeled oligonucleotide probe.