Recurrent gene fusions in prostate cancer

• US 9,938,582 B2
• Filed: 09/15/2010
• Issued: 04/10/2018
• 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
• Primary Examiner(s): SALMON, KATHERINE D
• Application Number:
  US12/882,533
• Publication Number:
  US 20110065113A1
• Time in Patent Office: 2,764 Days
• Field of Search: None
• 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 detecting in a human biological sample a solute carrier family 45, member 3 (SLC45A3):

rapidly accelerated fibrosarcoma (RAF) family member gene fusion, the method comprising;

a) forming a hybridized structure comprising;

i) a nucleic acid comprising a SLC45A3;

RAF family member gene fusion comprising a 5′

portion joined at a fusion junction to a 3′

portion, said 5′

portion of the gene fusion comprising at least 10 nucleotides from exon 1 of a SLC45A3 gene and said 3′

portion of the gene fusion comprising a human RAF kinase domain; and

ii) a detectably labeled probe specifically hybridized to said nucleic acid and spanning said fusion junction; and

b) detecting the presence of the SLC45A3;

RAF family member gene fusion in the human biological sample by detecting said hybridized structure in said human biological sample.

2. The method of claim 1 wherein said nucleic acid comprising said gene fusion comprises a chromosomal rearrangement of genomic DNA.

3. The method of claim 1 wherein said nucleic acid comprising said gene fusion is a chimeric mRNA transcript.

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

5. The method of claim 1, wherein the human RAF kinase domain is from a RAF family member gene selected from the group consisting of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and v-raf-1 murine leukemia viral oncogene homolog 1 (RAFT).

6. The method of claim 1 further comprising having a patient treated with a rapidly accelerated fibrosarcoma (RAF) inhibitor or a mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway inhibitor, wherein said patient is the source of said human biological sample comprising the SLC45A3:

RAF family member gene fusion.