Detection of Extracellular Tumor-Associated Nucleic Acid in Blood Plasma or Serum

Abstract

This invention relates to detection of specific extracellular DNA in plasma or serum fractions of human or animal blood associated with neoplastic, pre-malignant or proliferative disease. Specifically, the invention relates to detection tumor-associated DNA, and to those methods of detecting and monitoring tumor-associated DNA found in the plasma or serum fraction of blood by using DNA extraction and amplification with or without enrichment for DNA. The invention allows the selection and monitoring of patients for various cancer therapies including receptor tyrosine kinase inhibitor therapies.

1 . A method of detecting DNA of a gene translocation or fusion in the plasma or serum of a human, wherein said gene translocation or fusion is an ALK gene translocation or fusion, the method comprising the steps of:
 a) extracting DNA from the plasma or serum of a human;   b) assaying a portion of the extracted DNA for DNA of a translocation or fusion of the ALK gene; and   c) detecting DNA corresponding to said translocation or fusion of the ALK gene, or an amplified product thereof.   
     
     
         2 . The method of  claim 1 , wherein step b) comprises amplifying said extracted DNA for an ALK gene translocation or fusion. 
     
     
         3 . The method of  claim 1 , wherein the DNA of an ALK gene translocation or fusion is one selected from the group comprising NPM-ALK DNA, EML4-ALK DNA, TPM3-ALK DNA, TFG-ALK DNA, and ATIC-ALK DNA. 
     
     
         4 . The method of  claim 1 , wherein the ALK gene translocation is associated with a cancer in said human. 
     
     
         5 . A method of evaluating the plasma or serum of a human for DNA of a gene translocation or fusion, wherein said translocation or fusion is an ALK gene translocation or fusion, the method comprising the steps of:
 a) extracting DNA from plasma or serum of a human;   b) assaying a portion of the extracted DNA for an ALK gene translocation or fusion; and   c) detecting for DNA corresponding to sn ALK gene translocation or fusion, whereby plasma or serum of a human is thereby evaluated for DNA of a gene translocation or fusion.   
     
     
         6 . The method of  claim 5 , wherein step b) comprises amplifying said extracted DNA for an ALK gene translocation or fusion. 
     
     
         7 . The method of  claim 5 , wherein the DNA of an ALK gene translocation or fusion is one selected from the group comprising NPM-ALK DNA, EML4-ALK DNA, TPM3-ALK DNA, TFG-ALK DNA, and ATIC-ALK DNA. 
     
     
         8 . The method of  claim 5 , wherein the ALK gene translocation is associated with a cancer in said human.