RAF gene fusions

• US 8,945,556 B2
• Filed: 11/18/2011
• Issued: 02/03/2015
• Est. Priority Date: 11/19/2010
• 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, Palanisamy, Nallasivam, Kalyana-Sundaram, Shanker
• Primary Examiner(s): Gussow, Anne
• Assistant Examiner(s): Brown, Mindy G
• Application Number:
  US13/300,063
• Publication Number:
  US 20120142549A1
• Time in Patent Office: 1,173 Days
• Field of Search: None
• US Class Current: 424/141.1
• CPC Class Codes: C12N 9/12 transferring phosphorus containing groups, e.g. kinases (2.7)
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Y 207/11001 Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase
• CPC Class Codes: G01N 2333/912 transferring phosphorus containing groups, e.g. kinases (2.7)
• CPC Class Codes: G01N 2333/91205 Phosphotransferases in general
• CPC Class Codes: G01N 33/5748 involving oncogenic proteins

Abstract

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

Claims

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

(a) an oligonucleotide probe that hybridizes to a junction of a chimeric genomic DNA or a chimeric mRNA, wherein a 5′

portion of the chimeric genomic DNA or the chimeric mRNA is from an AGTRAP gene and a 3′

portion of the chimeric genomic DNA or the chimeric mRNA is from a RAF family member gene;

(b) an antibody specific for a fusion protein having an amino-terminal portion encoded by an angiotensin II, type I receptor-associated protein (AGTRAP) gene and a carboxy-terminal portion encoded by a kinase domain of a RAF family member gene.

2. The composition of claim 1 wherein the RAF family member gene is BRAF.

3. The composition of claim 1 wherein the carboxy-terminal portion of the fusion protein comprises a wild-type sequence of a RAF family member gene.

4. The composition of claim 1 further comprising the fusion protein having an amino-terminal portion encoded by an AGTRAP gene and a carboxy-terminal portion encoded by a kinase domain of a RAF family member gene.

5. The composition of claim 1 wherein the fusion protein having an amino-terminal portion encoded by an AGTRAP gene and a carboxy-terminal portion encoded by a RAF family member gene differs from the native AGTRAP protein or the native RAF family member gene in amino acid sequence;

post-translational processing; and

/or secondary, tertiary, or quaternary structure.

6. The composition of claim 1 wherein the antibody is labeled.

7. The composition of claim 1 wherein the antibody is polyclonal, monoclonal, chimeric, humanized, single chain, a Fv fragment, or a Fab fragment.

8. The composition of claim 1 wherein the antibody is linked to a bead.

9. The composition of claim 1 wherein the fusion protein comprises exon 5 of AGTRAP.

10. The composition of claim 1 wherein the fusion protein comprises exon 8 of BRAF.

11. The composition of claim 1 wherein the fusion protein comprises exon 8 of BRAF fused to exon 5 of AGTRAP.