Free circulating dna bio-markers and their applications

Abstract

This invention relates generally to methods for detecting cell damage as a consequence of pathophysiological or traumatic insults such as in a nuclear accident, bioterror attack, tumorigenesis, infections or in individuals with cardiovascular disease.

1 . A method for detecting cell damage related to a pathophysiological insult in a subject comprising
 detecting the presence or absence of a free circulating generic biomarker in a biological sample of the subject,
 wherein the detection is without nucleic acid amplification and 
 wherein the presence of the free circulating generic biomarker is indicative of cell damage related to a pathophysiological insult in the subject. 
   
     
     
         2 . The method of  claim 1 , wherein the biomarker is selected from the group consisting of Alu, 18S/28S, and telomere. 
     
     
         3 . The method of  claim 1 , wherein the detection is carried out using method selected from the group consisting of QuantiGene™ method, real-time PCR, quantitative PCR, fluorescent PCR, RT-MSP (RT methylation specific polymerase chain reaction), PicoGreen™ detection of DNA, radioimmunoassay, and direct radio-labeling of DNA. 
     
     
         4 . The method of  claim 1 , wherein the biological sample is a blood sample, serum sample, or a plasma sample. 
     
     
         5 . The method of  claim 1 , wherein the cell damage is related to necrosis or programmed cell death. 
     
     
         6 - 9 . (canceled) 
     
     
         10 . A method for detecting cell damage related to a pathophysiological insult in a subject comprising
 detecting the presence or absence of a free circulating generic biomarker in a biological sample of the subject,
 wherein the presence of the free circulating generic biomarker is indicative of cell damage related to a pathophysiological insult in the subject and wherein the pathophysiological insult is not cancer. 
   
     
     
         11 . The method of  claim 10 , wherein the pathophysiological insult is selected from the group consisting of radiation, autoimmune diseases, infection and cardiac infarction. 
     
     
         12 . The method of  claim 10 , wherein the pathophysiological insult is necrosis or cell death. 
     
     
         13 . The method of  claim 10 , wherein the biomarker is selected from the group consisting of Alu, 18S/28S, and telomere. 
     
     
         14 . The method of  claim 10 , wherein the detection is without nucleic acid amplification. 
     
     
         15 - 25 . (canceled) 
     
     
         26 . A method for detecting cell damage related to a pathophysiological insult in a subject comprising
 determining an expression profile of a free circulating generic biomarker in a biological sample of the subject,   wherein the expression profile is indicative of cell damage related to a particular pathophysiological insult in the subject among a group of possible pathophysiological insults consisting of cancer, radiation, autoimmune diseases, infection, and   
       cardiac infarction. 
     
     
         27 . The method of  claim 26 , wherein the expression profile comprises at least a characteristic selected from the group consisting of concentration, timeline, rate of increase, rate of resolution to baseline, peak level, differential expression of different generic markers, and time dependant changes in the differential expression of different generic markers. 
     
     
         28 . The method of  claim 26 , wherein the biomarker is selected from the group consisting of Alu, 18S/28S, and telomere. 
     
     
         29 . The method of  claim 26 , wherein the determination of the expression profile is without nucleic acid amplification. 
     
     
         30 - 40 . (canceled) 
     
     
         41 . A kit comprising a probe set useful for detection of Alu biomarker using QuantiGene™ method, wherein the probe set comprises a capture extender selected from the group consisting of SEQ ID NO. 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and 19, and the label extender is selected from the group consisting of SEQ ID NO. 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 and 44. 
     
     
         42 - 48 . (canceled)