Method for Monitoring Disease Progression or Recurrence

Abstract

The invention provides methods for detecting and monitoring diseases associated with genetic abnormalities in a subject.

1 . A method for monitoring disease progression or recurrence in a patient, the method comprising the steps of: interrogating one or more target nucleic acids in a first biological sample obtained from a patient for the presence of genetic indicia associated with a disease; determining the identity of at least one genetic abnormality that is present in the first biological sample and that is associated with the disease; and interrogating a second biological sample obtained at a later time for the presence of the genetic abnormality, wherein the presence or the amount of the genetic abnormality in the second biological sample is indicative of the progression or recurrence of the disease in the patient. 
     
     
         2 . The method of  claim 1 , wherein the first biological sample is a stool, blood, plasma, or serum sample. 
     
     
         3 . The method of  claim 1 , wherein the first biological sample is a tissue biopsy sample. 
     
     
         4 . The method of  claim 1 , wherein the second biological sample is a stool, blood, plasma, or serum sample. 
     
     
         5 . The method of  claim 1 , wherein the disease is the presence of an adenoma, cancer, precancer, or tumor in the patient. 
     
     
         6 . The method of  claim 5 , wherein the disease is colon, breast, or prostate cancer. 
     
     
         7 . The method of  claim 1 , further comprising the step of treating the patient between the times at which the first and second biological samples are obtained. 
     
     
         8 . The method of  claim 7 , wherein the treating comprises administering of a chemotherapeutic drug. 
     
     
         9 . The method of  claim 7 , wherein the treating comprises surgery. 
     
     
         10 . The method of  claim 9 , wherein the surgery is a colon resection. 
     
     
         11 . The method of  claim 7 , wherein the treating comprises radiation. 
     
     
         12 . The method of  claim 1 , wherein the one or more target nucleic acids are isolated from the biological sample using hybrid capture. 
     
     
         13 . The method of  claim 12 , wherein the hybrid capture comprises reversed-field electrophoresis. 
     
     
         14 . The method of  claim 1 , wherein said interrogating of said first biological sample comprises an assay the interrogates a plurality of tumor markers. 
     
     
         15 . The method of  claim 14 , wherein said plurality of tumor markers has a sensitivity of at least 80%. 
     
     
         16 . The method of  claim 1 , wherein said interrogating of said first biological sample comprises an assay that detects a nucleic acid sequence substitution, deletion, insertion or alteration in nucleic acid stability in a nucleic acid stability assay. 
     
     
         17 . The method of  claim 14 , wherein said plurality of tumor markers has a sensitivity of at least 85%. 
     
     
         18 . The method of  claim 14 , wherein said plurality of tumor markers has a sensitivity of at least 90%. 
     
     
         19 . The method of  claim 14 , wherein said plurality of tumor markers has a sensitivity of at least 95%. 
     
     
         20 . The method of  claim 14 , wherein said plurality of tumor markers has a sensitivity of at least 97%. 
     
     
         21 . The method of  claim 14 , wherein said plurality of tumor markers has a sensitivity of at least 98%. 
     
     
         22 . The method of  claim 14 , wherein said plurality of tumor markers has a sensitivity of at least 99%. 
     
     
         23 . The method of  claim 1 , wherein said disease is a tumor selected from the group consisting of colorectal cancer, breast cancer, lung cancer, prostate cancer, bladder cancer, colorectal cancer, pancreatic cancer, gastric cancer, breast cancer, ovarian cancer, endometrial, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, lymphoma, and leukemia. 
     
     
         24 . The method of  claim 23 , wherein said tumor is a colorectal tumor. 
     
     
         25 . The method of  claim 1 , wherein said interrogating of said first biological sample can detect at least one mutation in an adenomatous polyposis coli (APC), p53, or K-ras gene, or can detect a microsatellite instability marker (BAT26), or a DNA integrity measurement above a threshold level indicative of the presence of a disease in the patient. 
     
     
         26 . The method of  claim 25 , wherein said interrogating can detect at least 5 mutations in an adenomatous polyposis coli (APC), p53, or K-ras gene and can detect a microsatellite instability marker (BAT-26), or a or a DNA integrity measurement above a threshold level indicative of the presence of a disease in the patient. 
     
     
         27 . The method of  claim 25 , wherein said interrogating can detect at least 10 mutations in an adenomatous polyposis coli (APC), p53, or K-ras gene and can detect a microsatellite instability marker (BAT-26), or a or a DNA integrity measurement above a threshold level indicative of the presence of a disease in the patient. 
     
     
         28 . The method of  claim 25 , wherein said interrogating can detect at least 15 mutations in an adenomatous polyposis coli (APC), p53, or K-ras gene and can detect a microsatellite instability marker (BAT-26), or a or a DNA integrity measurement above a threshold level indicative of the presence of a disease in the patient. 
     
     
         29 . The method of  claim 1 , wherein said first and second biological samples are independently plasma, serum, cerbrospinal fluid, lymph, tear, semen, urine, sweat, sputum, bronchiolar lavage, a buccal swab product, or cervical smear. 
     
     
         30 . The method of  claim 1 , wherein said first and second biological samples are independently serum or plasma. 
     
     
         31 . The method of  claim 1 , wherein said interrogating comprises allele-specific PCR. 
     
     
         32 . The method of  claim 1 , wherein said interrogating comprises mismatch amplification mutation analysis. 
     
     
         33 . A method for monitoring the recurrence of a tumor in a subject, the method comprising contacting a sample from a subject with a plurality of tumor markers; diagnosing the presence of a tumor in said subject based on the presence of at least one tumor marker from said plurality; treating said tumor; and testing with said at least one tumor marker a biological sample from said patient, thereby monitoring the recurrence of a tumor in said subject.