Diagnostic Method Using PALB2/US

Abstract

The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.

We claim: 
     
         1 . A method comprising:
 analyzing a PALB2 nucleic acid or encoded protein from a sample obtained from a human diagnosed as having pancreatic cancer or identified as having an increased risk of pancreatic cancer; and   determining the presence or absence of a mutation in the PALB2 nucleic acid or encoded protein.   
     
     
         2 . The method of  claim 1  wherein the human is identified as having increased risk due to a family history of pancreatic cancer. 
     
     
         3 . The method of  claim 1  wherein the human has been diagnosed as having pancreatic cancer. 
     
     
         4 . The method of  claim 1  wherein a nucleic acid is analyzed and said nucleic acid is genomic DNA. 
     
     
         5 . The method of  claim 1  wherein said an encoded protein is analyzed. 
     
     
         6 . A method of diagnosing a predisposition to pancreatic cancer in a human, comprising:
 detecting in a non-tumor sample obtained from a human, a germline mutation in the PALB2 gene or its encoded protein, wherein the presence of the germline mutation indicates a predisposition to pancreatic cancer.   
     
     
         7 . The method of  claim 6  wherein said detecting step comprises analyzing a genomic DNA in said non-tumor sample. 
     
     
         8 . The method of  claim 6  wherein said detecting step comprises analyzing PALB2 protein in said sample. 
     
     
         9 . The method of  claim 6  wherein said individual is diagnosed as having pancreatic cancer, or is suspected of having pancreatic cancer, or has a family history of pancreatic cancer. 
     
     
         10 . A method of predicting an individual human's response to therapy, comprising:
 analyzing a sample obtained from an individual human,   detecting in the sample presence or absence of a mutation in the PALB2 gene or its encoded protein, wherein the presence of the mutation indicates that said individual has an increased likelihood of responding to a therapy that induces DNA damage or interferes with DNA damage repairs in tumor cells.   
     
     
         11 . The method of  claim 10  wherein said therapy is radiation therapy. 
     
     
         12 . The method of  claim 10  wherein said therapy is a DNA damaging agent. 
     
     
         13 . The method of  claim 10  wherein said therapy is an inhibitor of a DNA repair enzyme. 
     
     
         14 . The method of  claim 10  wherein said therapy comprises treatment with a PARP inhibitor. 
     
     
         15 . The method of  claim 10  wherein said sample is a normal tissue sample or a tumor sample. 
     
     
         16 . The method of  claim 10  wherein the individual human has a family history of pancreatic cancer. 
     
     
         17 . A method of treating pancreatic cancer in a patient comprising:
 administering to a patient identified as having a germline or somatic mutation in a PALB2 gene, a therapy that induces DNA damage or interferes with DNA damage repairs in tumor cells.   
     
     
         18 . A method of treating cancer, comprising:
 determining in a patient diagnosed as having pancreatic cancer the presence or absence of a defect in a PALB2 gene or encoded protein; and   if said defect is present, treating said patient with a therapeutic regimen that induces DNA damage or interferes with DNA damage repairs in tumor cells.