Recurrent gene fusions in prostate cancer

• US 20090208937A1
• Filed: 07/06/2007
• Published: 08/20/2009
• 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., Tomlins, Scott
• Granted Patent: US 10,041,123 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 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 identifying prostate cancer in a patient comprising:

(a) providing a sample from the patient; and

(b) detecting the presence or absence in the sample of a gene fusion having a 5′

portion from a transcriptional regulatory region of an androgen regulated gene defined as SLC45A3, HERV-K_—

22q1.23 or C15ORF21 and a 3′

portion from an ETS family member gene,

wherein detecting the presence in the sample of the gene fusion is indicative of identifies prostate cancer in the patient.

2. The method of claim 1, wherein the transcriptional regulatory region of the androgen regulated gene comprises a promoter region of the androgen regulated gene.

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

4. The method of claim 1, wherein step (b) comprises detecting chromosomal rearrangements of genomic DNA having a 5′

DNA portion from the transcriptional regulatory region of the androgen regulated gene and a 3′

DNA portion from the ETS family member gene.

10. The method of claim 1, wherein step (b) comprises detecting chimeric mRNA transcripts having a 5′

RNA portion transcribed from the transcriptional regulatory region of the androgen regulated gene and a 3′

RNA portion transcribed from the ETS family member gene.

16. The method of claim 1, wherein the sample is tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions or prostate cells.

5-9. -9. (canceled)

11-15. -15. (canceled)

17. A method for identifying prostate cancer in a patient comprising:

(a) providing a sample from the patient; and

(b) detecting the presence or absence in the sample of a gene fusion having a 5′

portion from a transcriptional regulatory region of a housekeeping gene and a 3′

portion from an ETS family member gene, wherein detecting the presence in the sample of the gene fusion identifies prostate cancer in the patient.

18. The method of claim 17, wherein the housekeeping gene is HNRPA2B1.

19. The method of claim 17, wherein the ETS family member gene is ETV1.

20. The method of claim 17, wherein the transcriptional regulatory region of the housekeeping gene comprises a promoter region of the housekeeping-gene.

21. The method of claim 17, wherein step (b) comprises detecting chromosomal rearrangements of genomic DNA having a 5′

DNA portion from the transcriptional regulatory region of the housekeeping gene and a 3′

DNA portion from the ETS family member gene.

27. The method of claim 17, wherein step (b) comprises detecting chimeric mRNA transcripts having a 5′

RNA portion transcribed from the transcriptional regulatory region of the housekeeping gene and a 3′

RNA portion transcribed from the ETS family member gene.

33. The method of claim 17, wherein the sample is tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions or prostate cells.

22-26. -26. (canceled)

28-32. -32. (canceled)

34. A method for identifying prostate cancer in a patient comprising:

(a) providing a sample from the patient; and

(b) detecting the presence or absence in the sample of a gene fusion having a 5′

portion from a transcriptional regulatory region of an androgen regulated gene and a 3′

portion from an ETV5 gene,

wherein detecting the presence in the sample of the gene fusion identifies prostate cancer in the patient.

35. The method of claim 34, wherein the androgen regulated gene is TMPRSS2 or SLC45A3.

36. The method of claim 34, wherein the transcriptional regulatory region of the androgen regulated gene comprises a promoter region of the androgen regulated gene.

37. The method of claim 34, wherein step (b) comprises detecting chromosomal rearrangements of genomic DNA having a 5′

DNA portion from the transcriptional regulatory region of the androgen regulated gene and a 3′

DNA portion from the ETV5 gene.

43. The method of claim 34, wherein step (b) comprises detecting chimeric mRNA transcripts having a 5′

RNA portion transcribed from the transcriptional regulatory region of the androgen regulated gene and a 3′

RNA portion transcribed from the ETV5 gene.

49. The method of claim 34, wherein the sample is tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions or prostate cells.

38-42. -42. (canceled)

44-48. -48. (canceled)

50. A composition comprising at least one of the following:

(a) an oligonucleotide probe comprising a sequence that hybridizes to a junction of a chimeric genomic DNA or chimeric mRNA in which a 5′

portion of the chimeric genomic DNA or chimeric mRNA is from a transcriptional regulatory region of a housekeeping gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from an ETS family member gene;

(b) a first oligonucleotide probe comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a housekeeping gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETS family member gene;

or

(c) a first amplification oligonucleotide comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a housekeeping gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETS family member gene.

51. A composition comprising at least one of the following:

(a) an oligonucleotide probe comprising a sequence that hybridizes to a junction of a chimeric genomic DNA or chimeric mRNA in which a 5′

portion of the chimeric genomic DNA or chimeric mRNA is from a transcriptional regulatory region of an SLC45A3 gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from an ETV1 gene;

(b) a first oligonucleotide probe comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of an SLC45A3 gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(c) a first amplification oligonucleotide comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of an SLC45A3 gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(d) an oligonucleotide probe comprising a sequence that hybridizes to a junction of a chimeric genomic DNA or chimeric mRNA in which a 5′

portion of the chimeric genomic DNA or chimeric mRNA is from a transcriptional regulatory region of a HERV-K_—

22q11.23 gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from an ETV1 gene;

(e) a first oligonucleotide probe comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a HERV-K_—

22q11.23 gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(f) a first amplification oligonucleotide comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a HERV-K_—

22q11.23 gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(g) an oligonucleotide probe comprising a sequence that hybridizes to a junction of a chimeric genomic DNA or chimeric mRNA in which a 5′

portion of the chimeric genomic DNA or chimeric mRNA is from a transcriptional regulatory region of a C15ORF21 gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from an ETV1 gene;

(h) a first oligonucleotide probe comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a C15ORF21 gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(i) a first amplification oligonucleotide comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a C15ORF21 gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(j) an oligonucleotide probe comprising a sequence that hybridizes to a junction of a chimeric genomic DNA or chimeric mRNA in which a 5′

portion of the chimeric genomic DNA or chimeric mRNA is from a transcriptional regulatory region of a HNRPA2B1 gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from an ETV1 gene;

(k) a first oligonucleotide probe comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a HNRPA2B1 gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(l) a first amplification oligonucleotide comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a HNRPA2B1 gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV1 gene;

(m) an oligonucleotide probe comprising a sequence that hybridizes to a junction of a chimeric genomic DNA or chimeric mRNA in which a 5′

portion of the chimeric genomic DNA or chimeric mRNA is from a transcriptional regulatory region of a TMPRSS2 gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV5 gene;

(n) a first oligonucleotide probe comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a TMPRSS2 gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV5 gene;

(O) a first amplification oligonucleotide comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of a TMPRSS2 gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV5 gene;

(p) an oligonucleotide probe comprising a sequence that hybridizes to a junction of a chimeric genomic DNA or chimeric mRNA in which a 5′

portion of the chimeric genomic DNA or chimeric mRNA is from a transcriptional regulatory region of a SLC45A3 gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from an ETV5 gene;

(q) a first oligonucleotide probe comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of an SLC45A3 gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV5 gene;

or

(r) a first amplification oligonucleotide comprising a sequence that hybridizes to a 5′

portion of a chimeric genomic DNA or chimeric mRNA from a transcriptional regulatory region of an SLC45A3 gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from an ETV5 gene.