Recurrent gene fusions in prostate cancer

Patent metadata

Field	Value
Publication number	US-9284609-B2
Application number	US-201213483157-A
Country	US
Kind code	B2
Filing date	May 30, 2012
Priority date	Sep 12, 2005
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

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

First claim

We claim:

1. A composition comprising an oligonucleotide probe covalently labeled with a detectable label and comprising a sequence that hybridizes to a junction of a chimeric nucleic acid molecule in which a 5′ portion of the chimeric nucleic acid molecule is from a TMPRSS2 gene and a 3′ portion of the chimeric nucleic acid molecule is from an ETS family member gene, wherein the ETS family member gene is selected from the group consisting of ERG, ETV1 (ER81), FLI1, ETS1, ETS2, ELK1, ETV6 (TEL1), ETV7 (TEL2), GABPa, ELF1, ETV4 (E1AF; PEA3), ETV5 (ERM), ERF, PEA3/E1AF, PU.1, ESE1/ESX, SAP1 (ELK4), ETV3(METS), EWS/FLI1, ESE1, ESE2 (ELF5), ESE3, PDEF, NET (ELK3; SAP2), NERF (ELF2), and FEV.

2. The composition of claim 1 , wherein the ETS family member gene is ERG.

3. The composition of claim 1 , wherein the ETS family member gene is ETV1.

4. The composition of claim 1 , wherein the ETS family member gene is FLI1.

5. The composition of claim 1 , wherein the ETS family member gene is ETV4.

6. The composition of claim 1 , wherein the 5′ portion of the chimeric nucleic acid molecule is from a transcriptional regulatory region of the TMPRSS2 gene.

7. The composition of claim 6 , wherein the transcriptional regulatory region comprises a promoter region of the TMPRSS2 gene.

8. A kit comprising the composition of claim 1 .

9. The kit of claim 8 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a prostate cancer antigen 3 (PCA3) nucleic acid molecule.

10. The kit of claim 8 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a prostate specific antigen (PSA) nucleic acid molecule.

11. The kit of claim 9 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a PSA nucleic acid molecule.

12. The kit of claim 8 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a nucleic acid molecule selected from one or more of the group consisting of PCA3, AMACR/P504S, PCGEM1, prostein/P501S, P503S, P504S, P509S, P510S, prostase/P703P, and P710P.

13. The kit of claim 10 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a nucleic acid molecule selected from one or more of the group consisting of PCA3, AMACR/P504S, PCGEM1, prostein/P501S, P503S, P504S, P509S, P510S, prostase/P703P, and P710P.

14. A kit comprising the composition of claim 2 .

15. The kit of claim 14 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a PCA3 nucleic acid molecule.

16. A composition comprising an oligonucleotide probe covalently labeled with a detectable label and comprising a sequence that hybridizes to a junction of a chimeric nucleic acid molecule in which a 5′ portion of the chimeric nucleic acid molecule is from a TMPRSS2 gene and a 3′ portion of the chimeric nucleic acid molecule is from an ERG gene.

17. The composition of claim 16 , wherein the 5′ portion of the chimeric nucleic acid molecule is from a transcriptional regulatory region of the TMPRSS2 gene.

18. The composition of claim 17 , wherein the transcriptional regulatory region comprises a promoter region of the TMPRSS2 gene.

19. A kit comprising the composition of claim 16 .

20. The kit of claim 19 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a PCA3 nucleic acid molecule.

21. The kit of claim 19 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a PSA nucleic acid molecule.

22. The kit of claim 19 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a nucleic acid molecule selected from one or more of the group consisting of PCA3, AMACR/P504S, PCGEM1, prostein/P501S, P503S, P504S, P509S, P510S, prostase/P703P, and P710P.

23. The kit of claim 21 , further comprising a detectably labeled oligonucleotide probe that hybridizes to a nucleic acid molecule selected from one or more of the group consisting of PCA3, AMACR/P504S, PCGEM1, prostein/P501S, P503S, P504S, P509S, P510S, prostase/P703P, and P710P.

Assignees

• Tomlins Scott
• Rhodes Daniel
• Chinnaiyan Arul
• Mehra Rohit
• Rubin Mark A
• Sun Xiao-Wei
• Perner Sven
• Lee Charles
• Demichelis Francesca
• Brigham & Womens Hospital
• Univ Michigan

Inventors

• Tomlins Scott
• Rhodes Daniel
• Chinnaiyan Arul
• Mehra Rohit
• Rubin Mark A
• Sun Xiao-Wei
• Perner Sven
• Lee Charles
• Demichelis Francesca

Classifications

• G01N33/57555

  of the prostate · CPC title

• A01K2267/0331

  Animal model for proliferative diseases · CPC title

• A01K2217/206

  Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase · CPC title

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title

• C12N9/6424

  Serine endopeptidases (3.4.21) · CPC title