RNA chimeras in human leukemia and lymphoma
Provided herein are kits, compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention relates to recurrent RNA fusions as diagnostic markers and clinical targets for leukemia.
1. A kit for detecting RNA fusions associated with B-cell chronic lymphocytic leukemia in a subject, comprising or consisting essentially of: at least a first RNA fusion informative reagent for identification of an YPEL5-PPP1CB and an PPP1CB-YPEL5 RNA fusion.
2. The kit of claim 1 , wherein said reagent is a probe that specifically hybridize to the fusion junction of an YPEL5-PPP1CB and an PPP1CB-YPEL5 RNA fusion, a pair of primers that amplify a fusion junction of an YPEL5-PPP1CB and an PPP1CB-YPEL5 RNA fusion, an antibody that binds to a truncated PPP1CB polypeptide, one or more sequencing primers that binds to a YPEL5-PPP1CB and an PPP1CB-YPEL5 RNA fusion and generate extension products that span the fusion junction of said YPEL5-PPP1CB and PPP1CB-YPEL5 RNA fusions, mass spectrometry reagents for identifying a truncated PPP1CB polypeptide, reagents for performing a PPP1CB activity assay, or a pair of probes wherein said first probe hybridizes to a YPEL5 nucleic acid and said second probe hybridizes to a PPP1CB nucleic acid.
3. The kit of claim 2 , wherein said pair of primers comprises a first primer that hybridizes to a YPEL5 nucleic acid and second primer that hybridizes to a PPP1CB nucleic acid.
4. The kit of claim 1 , further comprising one or more control nucleic acids.
5. The kit of claim 4 , wherein said controls comprise mRNA fusions or cDNA equivalents thereof.
6. The kit of claim 1 , wherein said reagent is labeled.
7. The kit of claim 1 , wherein said YPEL5-PPP1CB RNA fusion comprises exon 1 of YPEL5 and exon 2 of PPP1CB.
8. The kit of claim 1 , wherein said YPEL5-PPP1CB RNA fusion encodes a truncated PPP1CB polypeptide.
9. The kit of claim 8 , wherein said truncated PPP1CB polypeptide consists of residue 29 to residue 327 of wild type PPP1CB.
10. The kit of claim 1 , wherein said PPP1CB-YPEL5 RNA fusion comprises exon 1 of PPP and exon 3 of YPEL5.
11. The kit of claim 1 , wherein said PPP1CB-YPEL5 RNA fusion encodes full-length wild-type YPEL5 protein.