Pik3ca fusions

Abstract

The invention provides PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) gene fusions, and fragments of those gene fusions. The invention further provides methods of diagnosing and treating diseases or disorders associated with PIK3CA fusions, such as conditions mediated by PIK3CA aberrant expression or activity, or overexpression of PIK3CA.

1 - 45 . (canceled) 
     
     
         46 . A method for detecting in a patient a PIK3CA gene fusion selected from TBL1XR1:PIK3CA and FNDC3B:PIK3CA, wherein the gene fusion results in aberrant activity or expression of PIK3CA or overexpression of PIK3CA, said method comprising:
 a) contacting a biological sample from the patient with an oligonucleotide that hybridizes under stringent conditions to the fusion junction of the PIK3CA gene fusion; and   b) detecting hybridization between the PIK3CA fusion and the oligonucleotide.   
     
     
         47 . The method of  claim 46 , wherein the oligonucleotide hybridizes under stringent conditions to:
 a) a fragment of SEQ ID NO:1 comprising nucleotides 136-145 of SEQ ID NO:1;   b) a fragment of SEQ ID NO:3 comprising 355-364 of SEQ ID NO:3; or   c) a complement of a) or b).   
     
     
         48 . The method of  claim 46 , wherein the patient is suffering from or susceptible to a cancer. 
     
     
         49 . The method of  claim 48 , wherein the cancer is chosen from breast cancer, uterine cancer, and prostate cancer. 
     
     
         50 . A method for treating cancer in a patient in which a PIK3CA gene fusion selected from TBL1XR1:PIK3CA and FNDC3B:PIK3CA has been detected, said method comprising administering to the patient a therapeutically effective amount of an agent that inhibits PIK3CA activity or expression of the PIK3CA gene fusion, wherein the PIK3CA gene fusion has been detected in the patient by a method comprising:
 a) contacting a biological sample from the patient with an oligonucleotide that hybridizes under stringent conditions to the fusion junction of the PIK3CA gene fusion; and   b) detecting hybridization between the PIK3CA fusion and the oligonucleotide.   
     
     
         51 . The method of  claim 50 , wherein the agent inhibits expression of the PIK3CA gene fusion and is an oligonucleotide that hybridizes under stringent conditions to:
 a) a fragment of SEQ ID NO:1 comprising nucleotides 136-145 of SEQ ID NO:1;   b) a fragment of SEQ ID NO:3 comprising 355-364 of SEQ ID NO:3; or   c) a complement of a) or b).   
     
     
         52 . The method of  claim 50 , wherein the patient is suffering from or susceptible to a cancer. 
     
     
         53 . The method of  claim 52 , wherein the cancer is chosen from breast cancer, uterine cancer, and prostate cancer. 
     
     
         54 . A method for diagnosing cancer in a patient comprising:
 a) contacting a biological sample from the patient with an oligonucleotide that hybridizes under stringent conditions to the fusion junction of the PIK3CA gene fusion; and   b) diagnosing the patient with cancer when hybridization of the oligonucleotide to the PIK3CA gene fusion is detected.   
     
     
         55 . An RNA molecule that hybridizes under stringent conditions to a nucleic acid encoding at least the fusion junction of a TBL1XR1:PIK3CA or FNDC3B:PIK3CA gene fusion. 
     
     
         56 . The RNA molecule of  claim 55 , wherein the RNA molecule inhibits aberrant expression or overexpression of PIK3CA. 
     
     
         57 . The RNA molecule of  claim 55 , wherein the RNA molecule hybridizes to a nucleic acid encoding:
 a) a fragment of SEQ ID NO:1 comprising nucleotides 136-145 of SEQ ID NO:1;   b) a fragment of SEQ ID NO:3 comprising 355-364 of SEQ ID NO:3; or   c) a complement of a) or b).