Recurrent gene fusions in prostate cancer

Patent metadata

Field	Value
Publication number	US-9745635-B2
Application number	US-201514864466-A
Country	US
Kind code	B2
Filing date	Sep 24, 2015
Priority date	Sep 12, 2005
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

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 a hybridized oligonucleotide:target gene fusion duplex, wherein the target gene fusion comprises 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), GABPα, 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; and wherein the oligonucleotide is covalently labeled with a detectable label.

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

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

4. The composition of claim 1 wherein the ETS family member gene is an ETV4 gene.

5. The composition of claim 1 wherein the ETS family member gene is an FLI1 gene.

6. The composition of claim 1 wherein the target gene fusion is obtained from a tissue, blood, urine, semen, prostatic secretion, plasma, serum, urine supernatant, urine cell pellet, or prostate cell sample.

7. 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.

8. The composition of claim 1 wherein the transcriptional regulatory region comprises a promoter region of the TMPRSS2 gene.

9. The composition of claim 1 wherein the oligonucleotide is hybridized to a junction at which the 5′ portion of the chimeric nucleic acid molecule is fused to the 3′ portion of the chimeric nucleic acid molecule.

10. The composition of claim 1 wherein:
a) the oligonucleotide is hybridized to the 5′ portion of the chimeric nucleic acid molecule and the composition further comprises a second oligonucleotide hybridized to the 3′ portion of the chimeric nucleic acid molecule; or
b) the oligonucleotide is hybridized to the 3′ portion of the chimeric nucleic acid molecule and the composition further comprises a second oligonucleotide hybridized to the 5′ portion of the chimeric nucleic acid molecule, wherein the second oligonucleotide is covalently labeled with a detectable label.

11. The composition of claim 10 further comprising a polymerase.

12. The composition of claim 10 further comprising a third oligonucleotide covalently labeled with a detectable label.

13. The composition of claim 1 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, PSA, AMACR/P504S, PCGEM1, prostein/P501S, P503S, P504S, P509S, P510S, prostase/P703P, and P710P.

14. The composition of claim 1 further comprising a detectably labeled oligonucleotide probe that hybridizes to PSA.

15. The composition of claim 1 further comprising a detectably labeled oligonucleotide probe that hybridizes to PCA3.

16. A method of producing a hybridized oligonucleotide:target gene fusion duplex, the method comprising contacting a sample comprising a target gene fusion comprising 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 with an oligonucleotide covalently labeled with a detectable label and having a sequence that hybridizes to a junction at which the 5′ portion of the chimeric nucleic acid molecule is fused to the 3′ portion of the chimeric nucleic acid molecule.

17. The method of claim 16 wherein the 5′ portion of the chimeric nucleic acid molecule is from a TMPRSS2 gene and the 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), GABPα, 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.

18. The method of claim 16 wherein the sample comprises tissue, blood, urine, semen, prostatic secretion, plasma, serum, urine supernatant, urine cell pellet, or a prostate cell.

Assignees

• Univ Michigan Regents
• Brigham & Womens Hospital Inc

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

• Y10S435/81

  Packaged device or kit · CPC title

• A01K2217/072

  maintaining or altering function, i.e. knock in · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N9/6424

  Serine endopeptidases (3.4.21) · CPC title