Recurrent gene fusions in prostate cancer

• US 8,580,509 B2
• Filed: 05/30/2012
• Issued: 11/12/2013
• Est. Priority Date: 09/12/2005
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated, Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Tomlins, Scott, Rhodes, Daniel, Chinnaiyan, Arul, Mehra, Rohit, Rubin, Mark A., Sun, Xiao-Wei, Perner, Sven, Lee, Charles, Demichelis, Francesca
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): Tung, Joyce
• Application Number:
  US13/483,176
• Publication Number:
  US 20120295809A1
• Time in Patent Office: 531 Days
• Field of Search: 435/6.12, 435/91.2, 435/810, 536/22.1, 536/24.3
• US Class Current: 435/6.12
• CPC Class Codes: A01K 2217/072 maintaining or altering function, i.e. knock in
• CPC Class Codes: A01K 2217/206 Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0331 Animal model for proliferative diseases
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• CPC Class Codes: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 15/113 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 Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 9/6424 Serine endopeptidases (3.4.21)
• CPC Class Codes: C12N 9/6445 Kallikreins (3.4.21.34; 3.4.21.35)
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• 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 2600/158 Expression markers
• CPC Class Codes: G01N 33/57434 of prostate
• CPC Class Codes: Y10S 435/81 : Packaged device or kit

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.

Claims

1. A method for identifying or characterizing prostate cancer in a subject comprising:

contacting a sample obtained from the subject, wherein the sample is selected from the group of consisting of prostate tissue, blood, urine, semen, prostatic secretions and prostate cells, with a nucleic acid diagnostic reagent, and detecting the presence, or determining the absence, in the sample of;

(a) a gene fusion having or resulting from the fusion of, rearrangement of, or genomic deletion between, a 5′

portion from a TMPRSS2 gene and a 3′

portion from an ETS family member gene, wherein the ETS family member gene is selected from the group consisting of ERG, ETV1, ETV4, and FLI1; and

(b) a PCA3 nucleic acid molecule,

wherein detecting the presence in the sample of the gene fusion and PCA3 identifies or characterizes prostate cancer in the subject.

2. The method of claim 1, wherein the 5′

portion from the TMPRSS2 gene comprises a transcriptional regulatory region of the TMPRSS2 gene.

3. The method of claim 2, wherein the transcriptional regulatory region comprises a promoter region.

4. The method of claim 1, further comprising detecting the presence, or determining the absence, in the sample of a prostate specific antigen (PSA) nucleic acid molecule.

5. The method of claim 1, further comprising detecting the presence, or determining the absence, in the sample of a nucleic acid molecule selected from one or more of the group consisting of AMACR/P504S, PCGEM1, prostein/P501S, P503S, P504S, P509S, P510S, prostase/P703P, and P710P.

6. The method of claim 5, further comprising detecting the presence, or determining the absence, in the sample of a PSA nucleic acid molecule.

7. The method of claim 1, wherein the characterizing prostate cancer comprises determining a presence or reoccurrence of prostate cancer in the subject.

8. The method of claim 1, wherein the characterizing prostate cancer comprises determining the type, progression, or aggressiveness of the prostate cancer.

9. The method of claim 1, further comprising any one or more of the following:

(a) diagnosing prostate cancer in the subject based on the detected presence of the gene fusion and PCA3 in the sample;

(b) determining a prognosis for the subject based on the detected presence of the gene fusion and PCA3 in the sample;

or

(c) selecting a therapeutic strategy for the subject based on the detected presence of the gene fusion and PCA3 in the sample.

10. A method for identifying or characterizing prostate cancer in a subject comprising:

detecting, if present, in a sample obtained from the subject, wherein the sample is selected from the group of consisting of prostate tissue, blood, urine, semen, prostatic secretions and prostate cells;

(a) a gene fusion having or resulting from the fusion of, rearrangement of, or genomic deletion between, a 5′

portion from a TMPRSS2 gene and a 3′

portion from an ERG gene; and

(b) a PCA3 nucleic acid molecule,

wherein detecting the presence in the sample of the gene fusion and PCA3 identifies or characterizes prostate cancer in the subject.

11. The method of claim 10, wherein the 5′

portion from the TMPRSS2 gene comprises a transcriptional regulatory region of the TMPRSS2 gene.

12. The method of claim 11, wherein the transcriptional regulatory region comprises a promoter region.

13. The method of claim 10, further comprising detecting the presence, or determining the absence, in the sample of a prostate specific antigen (PSA) nucleic acid molecule.

14. The method of claim 10, further comprising detecting the presence, or determining the absence, in the sample of a nucleic acid molecule selected from one or more of the group consisting of AMACR/P504S, PCGEM1, prostein/P501S, P503S, P504S, P509S, P510S, prostase/P703P, and P710P.

15. The method of claim 14, further comprising detecting the presence, or determining the absence, in the sample of a PSA nucleic acid molecule.

16. The method of claim 10, wherein the characterizing prostate cancer comprises determining a presence or reoccurrence of prostate cancer in the subject.

17. The method of claim 10, wherein the characterizing prostate cancer comprises determining the type, progression, or aggressiveness of the prostate cancer.

18. The method of claim 10, further comprising any one or more of the following:

(a) diagnosing prostate cancer in the subject based on the detected presence of the gene fusion and PCA3 in the sample;

(b) determining a prognosis for the subject based on the detected presence of the gene fusion and PCA3 in the sample;

or

(c) selecting a therapeutic strategy for the subject based on the detected presence of the gene fusion and PCA3 in the sample.