RECURRENT GENE FUSIONS IN PROSTATE CANCER

• US 20110065113A1
• Filed: 09/15/2010
• Published: 03/17/2011
• Est. Priority Date: 09/17/2009
• 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., Wang, Xiaosong
• Granted Patent: US 9,938,582 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 2600/118 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: G01N 2800/7028 Cancer

Abstract

The present invention relates to compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention relates to recurrent gene fusions as diagnostic markers and clinical targets for prostate cancer.

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 SLC45A3 gene and a 3′

portion from a RAF family gene,

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

2. The method of claim 1, wherein the transcriptional regulatory region of the SLC45A3 gene comprises a promoter region of the SLC45A3 gene.

3. 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 SLC45A3 gene and a 3′

DNA portion from the RAF family gene.

4. 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 SLC45A3 gene and a 3′

RNA portion transcribed from a RAF family gene.

5. The method of claim 1, wherein the sample is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions and prostate cells.

6. The method of claim 1, wherein said RAF family member gene is selected from the group consisting of BRAF and RAF1.

7. 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 UBE2L3 gene and a 3′

portion from a RAS family gene,

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

8. The method of claim 7, wherein the transcriptional regulatory region of the UBE2L3 gene comprises a promoter region of the UBE2L3 gene.

9. The method of claim 7, wherein step (b) comprises detecting chromosomal rearrangements of genomic DNA having a 5′

DNA portion from the transcriptional regulatory region of the UBE2L3 gene and a 3′

DNA portion from the RAS family gene.

10. The method of claim 7, wherein step (b) comprises detecting chimeric mRNA transcripts having a 5′

RNA portion transcribed from the transcriptional regulatory region of the UBE2L3 gene and a 3′

RNA portion transcribed from a RAS family gene.

11. The method of claim 7, wherein the sample is selected from the group consisting of tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions and prostate cells.

12. The method of claim 7, wherein said RAS family member gene is KRAS.

13. 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 a RAF 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 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 a RAF family member 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 a RAF family member 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 an UBE2L3 gene and a 3′

portion of the chimeric genomic DNA or chimeric mRNA is from a RAS family member 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 an UBE2L3 gene and a second oligonucleotide probe comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from a RAS family member 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 an UBE2L3 gene and a second amplification oligonucleotide comprising a sequence that hybridizes to a 3′

portion of the chimeric genomic DNA or chimeric mRNA from a RAS family member gene; and

(g) an antibody to a chimeric protein having an amino-terminal portion encoded by the UBE2L3 gene and a carboxy-terminal portion encoded by a RAS family member gene.

14. The composition of claim 13, wherein said RAF family member gene is selected from the group consisting of BRAF and RAF1.

15. The composition of claim 13, wherein said RAS family member gene is KRAS.