Methods for disease detection

Abstract

The present invention provides methods for detecting disease by analysis of a patient sample to determine the integrity of nucleic acids in the sample.

What is claimed is:  
     
         1 . A method for determining the disease status of a patient, the method comprising the steps of: 
 determining the integrity of nucleic acids in a patient sample comprising shed cells or cellular debris; and    identifying said patient as having disease if intact nucleic acids are present in said sample in an amount greater than a predetermined threshold.    
     
     
         2 . A method for screening a patient for disease, the method comprising the steps of: 
 determining the integrity of nucleic acids in a patient sample comprising shed cellular debris; and    Identifying a positive screen as a sample in which the integrity of nucleic acids exceeds a predetermined threshold.    
     
     
         3 . A method for detecting disease in a patient, the method comprising the steps of: 
 determining an amount of patient nucleic acid present in a patient sample;    comparing said amount with a standard amount of nucleic acid expected to be present in a disease-negative sample; and    detecting disease in said patient as an amount of patient nucleic acid greater than said standard amount.    
     
     
         4 . The method of  claim 3 , wherein said nucleic acid is a fragment having a molecular weight of at least 1.3 Kb.  
     
     
         5 . The method of  claim 1 , wherein said disease is cancer or pre-cancer.  
     
     
         6 . The Method of  claim 3 , wherein said cancer is selected from the group consisting of colon cancer, lung cancer, esophageal cancer, prostate cancer, stomach cancer, pancreatic cancer, liver cancer, and lymphoma.  
     
     
         7 . The method of  claim 1 , wherein said nucleic acid is selected from the group consisting of K-ras, p53, apc, dcc, tumor suppressor genes, and oncogenes.  
     
     
         8 . The method of  claim 1 , wherein said patient sample is selected from the group consisting of stool, sputum, pancreatic fluid, bile, lymph, blood, urine, cerebrospinal fluid, seminal fluid, saliva, breast nipple aspirate, and pus.  
     
     
         9 . A method for screening a patient sample to determine the disease status of a patient, the method comprising the steps of: 
 (a) amplifying patient nucleic acid in a sample obtained from a patient;    (b) determining an amount of amplified nucleic acid obtained in Step (a); and    (c) identifying a positive screen when said amount of amplified nucleic acid is greater than an amount of amplified nucleic acid expected in a disease-negative sample.    
     
     
         10 . A method for screening a biological sample for disease, the method comprising the steps of: 
 selecting a plurality of genomic loci;    conducting an amplification reaction at each of said loci;    identifying a positive screen as a sample in which the number of loci producing an amplification product exceeds a predetermined threshold.    
     
     
         11 . A method for screening a patient sample for disease, the method comprising the steps of: 
 selecting a plurality of genomic loci;    conducting an amplification reaction at each of said loci;    assigning a first numerical score to each locus in which amplification takes place;    assigning a second numerical score to each locus in which amplification does not take place;    determining whether a total of said first numerical score exceeds a total of said second numerical score by a threshold amount, thereby to screen said sample for disease.    
     
     
         12 . A nucleic acid fragment isolated from a patient sample, said nucleic acid being at least 1.3 Kb and indicative of nucleic acid integrity associated with cancer.  
     
     
         13 . An isolated nucleic acid obtained by the method of  claim 1.