Recurrent gene fusions in prostate cancer

Patent metadata

Field	Value
Publication number	US-10190173-B2
Application number	US-201615149780-A
Country	US
Kind code	B2
Filing date	May 9, 2016
Priority date	Sep 12, 2005
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

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 fluorescence in situ hybridization (FISH) method for detecting an ARG-ETS gene fusion in a sample from a subject, the method comprising:
(a) hybridizing a directly labeled FISH probe to an ARG-ETS gene fusion comprising a 5′ portion fused to a 3′ portion, said 5′ portion from an ARG gene selected from the group consisting of PSA and TMPRSS2 and said 3′ portion from an ETS family member gene 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
(b) detecting the presence of the ARG-ETS gene fusion in the sample from the subject by detecting hybridization of the directly labeled FISH probe to a junction at which the 5′ portion of the gene fusion fuses to the 3′ portion of the gene fusion.

2. The FISH method of claim 1 wherein the ETS gene is ERG.

3. The FISH method of claim 1 wherein the ARG is TMPRSS2.

4. The FISH method of claim 1 wherein the ARG-ETS gene fusion comprises exon 4 of ERG, exon 2 of ERG, and/or exon 1 of TMPRSS2.

5. A FISH method for detecting an ARG-ETS gene fusion in a sample from a subject, the method comprising:
(a) hybridizing a first directly labeled FISH probe and a second directly labeled FISH probe to an ARG-ETS gene fusion comprising a 5′ portion fused to a 3′ portion, said 5′ portion from an ARG gene selected from the group consisting of PSA and TMPRSS2 and said 3′ portion from an ETS family member gene 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
(b) detecting the presence of the ARG-ETS gene fusion in the sample from the subject by detecting hybridization of the first directly labeled FISH probe to the 5′ portion of the gene fusion and detecting hybridization of the second directly labeled FISH probe to the 3′ portion of the gene fusion.

6. The FISH method of claim 5 wherein the ETS gene is ERG.

7. The FISH method of claim 5 wherein the ARG is TMPRSS2.

8. A composition for FISH analysis of a sample from a subject, the composition comprising a directly labeled FISH probe comprising a sequence capable of hybridizing to a fusion junction of an ARG-ETS gene fusion, wherein said ARG-ETS gene fusion comprises a 5′ portion fused to a 3′ portion, said 5′ portion is from an ARG gene selected from the group consisting of PSA and TMPRSS2, and said 3′ portion is from an ETS family member gene selected from the group consisting of ERG, ETV1 (ER81), FLIT, 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.

9. The composition of claim 8 wherein the ETS gene is ERG.

10. The composition of claim 8 wherein the ARG is TMPRSS2.

11. A composition for FISH analysis of a sample from a subject, the composition comprising a first directly labeled FISH probe capable of hybridizing to a 5′ portion of an ARG-ETS gene fusion and a second directly labeled FISH probe capable of hybridizing to the 3′ portion of the ARG-ETS gene fusion, wherein said ARG-ETS gene fusion comprises a 5′ portion fused to a 3′ portion, said 5′ portion is from an ARG gene selected from the group consisting of PSA and TMPRSS2, and said 3′ portion is from an ETS family member gene 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.

12. The composition of claim 11 wherein the ETS gene is ERG.

13. The composition of claim 11 wherein the ARG is TMPRSS2.

14. A kit for FISH analysis of a sample from a subject, the kit comprising a directly labeled FISH probe comprising a sequence capable of hybridizing to a fusion junction of an ARG-ETS gene fusion, wherein said ARG-ETS gene fusion comprises a 5′ portion fused to a 3′ portion, said 5′ portion is from an ARG gene selected from the group consisting of PSA and TMPRSS2, and said 3′ portion is from an ETS family member gene 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.

15. A kit for FISH analysis of a sample from a subject, the kit comprising a first directly labeled FISH probe capable of hybridizing to a 5′ portion of an ARG-ETS gene fusion and a second directly labeled FISH probe capable of hybridizing to the 3′ portion of the ARG-ETS gene fusion, wherein said ARG-ETS gene fusion comprises a 5′ portion fused to a 3′ portion, said 5′ portion is from an ARG gene selected from the group consisting of PSA and TMPRSS2, and said 3′ portion is from an ETS family member gene 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.

16. A system for FISH analysis of a sample from a subject, the system comprising:
a) one or more probe sets that comprise:
i) a directly labeled FISH probe comprising a sequence capable of hybridizing to a fusion junction of an ARG-ETS gene fusion, wherein said ARG-ETS gene fusion comprises a 5′ portion fused to a 3′ portion, said 5′ portion is from an ARG gene selected from the group consisting of PSA and TMPRSS2, and said 3′ portion is from an ETS family member gene 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; or
ii) a first directly labeled FISH probe capable of hybridizing to a 5′ portion of an ARG-ETS gene fusion and a second directly labeled FISH probe capable of hybridizing to the 3′ portion of the ARG-ETS gene fusion, wherein said ARG-ETS gene fusion comprises a 5′ portion fused to a 3′ portion, said 5′ portion is from an ARG gene selected from the group consisting of PSA and TMPRSS2, and said 3′ portion is from an ETS family member gene 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

b) a means for detecting directly labeled FISH probes in the sample.

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

• C12Q2600/156

  Polymorphic or mutational markers · 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

• A01K2227/105

  Murine · CPC title

• A01K2267/0331

  Animal model for proliferative diseases · CPC title