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.

1 .- 3 . (canceled) 
     
     
         4 . A method for monitoring cancer or precancer progression in a patient, the method comprising the steps of:
 (a) detecting in a first biological sample and in a later obtained second biological sample from a patient an amount of a long nucleic acid of length 200 base pairs or longer;   (b) comparing the amount of long nucleic acid from said first sample to said second sample to assess structural integrity of nucleic acids in the samples; and   (c) monitoring whether a cancer or precancer is progressing or receding by determining whether the structural integrity in said second sample is increasing or decreasing, wherein an increase in the structural integrity of nucleic acids over time is indicative of cancer or precancer progression.   
     
     
         5 . The method of  claim 4 , wherein in step (c) the patient presents no or minimal symptoms and an increase in structural integrity of nucleic acids over time indicates cancer or precancer progression. 
     
     
         6 . The method of  claim 4 , wherein the biological sample comprises shed cells or cellular debris. 
     
     
         7 . The method of  claim 4 , wherein the biological sample is selected from the group consisting of stool, sputum, urine, bile, pancreatic juice, and blood samples. 
     
     
         8 . The method of  claim 4 , wherein in the biological sample is a stool sample. 
     
     
         9 . The method of  claim 4 , wherein in step (a) the amount of long nucleic acid is 400 base pairs or longer in length. 
     
     
         10 . The method of  claim 4 , wherein in step (a) the amount of long nucleic acid is 800 base pairs or longer in length. 
     
     
         11 . The method of  claim 4 , wherein in step (a) the amount of long nucleic acid is 1.3 Kb or longer in length. 
     
     
         12 . The method of  claim 4 , wherein in step (a) the amount of long nucleic acid is 1.8 Kb or longer in length. 
     
     
         13 . The method of  claim 4 , wherein in step (a) the amount of long nucleic acid is 2.4 or longer in length. 
     
     
         14 . The method of  claim 4 , wherein the cancer or precancer is selected from the group consisting of lung cancer, esophageal cancer, prostate cancer, stomach cancer, pancreatic cancer, liver cancer, cancer of the bile duct, cancer of the duodenum, lymphoma, and colorectal cancer. 
     
     
         15 . The method of  claim 4 , wherein the cancer or precancer is colorectal cancer. 
     
     
         16 . A method for monitoring cancer or precancer progression, the method comprising the steps of:
 (a) conducting on a series of biological samples derived from a patient over time either:
 (i) at least two amplification reactions at a single genomic locus, wherein each reaction is designed to amplify a nucleic acid fragment of a different length between 200 base pairs to 2.4 Kb or longer; or 
 (ii) at least two amplification reactions at at least two different genomic loci, wherein each reaction is designed to amplify a nucleic acid having the same length, the length of the fragment being 200 base pairs to 2.4 Kb or longer; 
   (b) measuring the amount of amplicon produced from the reaction in step (a) to assess the structural integrity of nucleic acids in the samples; and   (c) monitoring whether a cancer or precancer is progressing or receding by determining whether the structural integrity in a sample is increasing or decreasing, wherein an increase in structural integrity over time is indicative of disease progression.   
     
     
         17 . The method of  claim 16 , wherein in step (c) the patient presents no or minimal symptoms and an increase in structural integrity of nucleic acids over time indicates cancer or precancer progression. 
     
     
         18 . The method of  claim 16 , wherein the biological sample comprises shed cells or cellular debris. 
     
     
         19 . The method of  claim 16 , wherein the biological sample is selected from the group consisting of stool, sputum, urine, bile, pancreatic juice, and blood samples. 
     
     
         20 . The method of  claim 16 , wherein the biological sample is a stool sample. 
     
     
         21 . The method of  claim 16 , wherein the cancer or precancer is selected from the group consisting of lung cancer, esophageal cancer, prostate cancer, stomach cancer, pancreatic cancer, liver cancer, cancer of the bile duct, cancer of the duodenum, lymphoma and colorectal cancer. 
     
     
         22 . The method of  claim 16 , wherein the cancer or precancer is colorectal cancer. 
     
     
         23 . A method for monitoring cancer or precancer progression in a patient, the method comprising the steps of:
 (a) determining in a biological sample obtained from a patient the amount of long nucleic acid of 200 base pairs or longer in length; and   (b) comparing the amount of long nucleic acid in the biological sample to a predetermined level of long nucleic acid from the patient, wherein an increase in the amount of long nucleic acid is indicative of cancer or precancer progression.