Method for monitoring disease progression or recurrence

• US 9,109,256 B2
• Filed: 10/27/2005
• Issued: 08/18/2015
• Est. Priority Date: 10/27/2004
• Status: Active Grant

• Current Assignee: Esoterix Genetic Laboratories LLC (Laboratory Corporation Of America Holdings)
• Original Assignee: Esoterix Genetic Laboratories LLC (Laboratory Corporation Of America Holdings)
• Inventors: Shuber, Anthony P.
• Primary Examiner(s): Martinell, James
• Application Number:
  US11/666,561
• Publication Number:
  US 20080161420A1
• Time in Patent Office: 3,582 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61B 5/4842 Monitoring progression or stage of a disease
• CPC Class Codes: A61B 5/4848 Monitoring or testing the effects of treatment, e.g. of medication
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/154 Methylation markers
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: Y10T 436/145555 Hetero-N

Abstract

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

Claims

1. A method for monitoring disappearance, regression, progression or recurrence of diseased tissue in a patient, the method comprising the steps of:

obtaining a first heterogeneous biological sample from the patient;

generating a patient-specific genetic profile of diseased tissue by interrogating a plurality of genomic loci in genomic DNA and/or free DNA isolated from the first heterogeneous biological sample obtained from the patient for the presence and/or the amount of a plurality of biomarkers, wherein

(i) the plurality of genomic loci comprises at least one mutation in each of K-ras, adenomatous polyposis coli (APC), p53, and PIK3CA, and

(ii) the presence of at least one mutation at an individual locus is indicative of the presence of diseased tissue; and

initiating a treatment protocol after the first heterogeneous biological sample is obtained;

obtaining a second heterogeneous biological sample from said patient after treatment; and

monitoring the patient-specific genetic profile by interrogating the plurality of genomic loci in genomic DNA and/or free DNA isolated from the second heterogeneous biological sample for the presence and/or the amount of the plurality of biomarkers, wherein a change of the patient-specific genetic profile is indicative of the disappearance, regression, progression or recurrence of the diseased tissue in the patient.

2. The method of claim 1, wherein the first heterogeneous biological sample is a stool, blood, plasma, serum, cerebrospinal fluid, lymph, tear, semen, urine, sweat, sputum, bronchiolar lavage, a buccal swab product, or cervical smear sample.

3. The method of claim 1, wherein the first heterogeneous biological sample is a tissue biopsy sample.

4. The method of claim 1, wherein the second heterogeneous biological sample is a stool, blood, plasma, serum, cerebrospinal fluid, lymph, tear, semen, urine, sputum, bronchiolar lavage, a buccal swab product, or cervical smear sample.

5. The method of claim 1, wherein the diseased tissue is associated with an adenoma, cancer, precancer, and/or tumor in the patient.

6. The method of claim 5, wherein the diseased tissue is associated with colon, breast, or prostate cancer.

7. The method of claim 1, wherein the treating step comprises administering of a chemotherapeutic drug.

8. The method of claim 1, wherein the treating step comprises surgery.

9. The method of claim 8, wherein the diseased tissue comprises colon cancer and the surgery is a colon resection.

10. The method of claim 1, wherein the treating step comprises radiation.

11. The method of claim 1, wherein the method comprises a step of isolating target nucleic acids containing the plurality of genomic loci from the heterogeneous biological sample using hybrid capture.

12. The method of claim 11, wherein the hybrid capture comprises reversed-field electrophoresis.

13. The method of claim 1, wherein the plurality of biomarkers comprise a plurality of tumor markers.

14. The method of claim 1, wherein the plurality of biomarkers has a sensitivity of detecting the disease of at least 80%.

15. The method of claim 1, wherein the plurality of biomarkers comprises a nucleic acid sequence substitution, deletion, and/or insertion.

16. The method of claim 1, wherein the plurality of biomarkers has a sensitivity of detecting the disease of at least 85%.

17. The method of claim 1, wherein the plurality of biomarkers has a sensitivity of detecting the disease of at least 90%.

18. The method of claim 1, wherein the plurality of biomarkers has a sensitivity of detecting the disease of at least 95%.

19. The method of claim 1, wherein the plurality of biomarkers has a sensitivity of detecting the disease of at least 97%.

20. The method of claim 1, wherein the diseased tissue is associated with 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.

21. The method of claim 20, wherein the tumor is a colorectal tumor.

22. The method of claim 1, wherein the one or more mutations comprise at least 5 mutations.

23. The method of claim 1, wherein the one or more mutations comprise at least 10 mutations.

24. The method of claim 1, wherein the one or more mutations comprise at least 15 mutations.

25. The method of claim 1, wherein the first and second biological samples are different types of samples.

26. The method of claim 1, wherein said first and/or second biological sample is serum or plasma.

27. The method of claim 1, wherein said interrogating comprises allele-specific PCR.

28. The method of claim 1, wherein said interrogating comprises mismatch amplification mutation analysis.

29. The method of claim 1, where in the plurality of genomic loci comprises at least 10 different loci.

30. The method of claim 29, wherein the plurality of genomic loci comprises at least 15 different loci.

31. The method of claim 30, wherein the plurality of genomic loci comprises at least 20 different loci.

32. The method of claim 31, wherein the plurality of genomic loci comprises at least 25 different loci.

33. The method of claim 1, further comprising a step of recommending a therapeutic decision based on the change in the patient specific genetic profile.

34. The method of claim 1, wherein the method further comprises evaluating if the treating step is effective for the disease based on the change in the patient specific genetic profile.

35. The method of claim 1, wherein said interrogating comprises digital assay analysis.

36. The method of claim 1, wherein said interrogating comprises high complexity sequence analysis.

37. The method of claim 1, wherein said interrogating comprises a quantification of the plurality of biomarkers.

38. A method for monitoring disappearance, regression, progression or recurrence of diseased tissue in a patient, the method comprising the steps of:

generating a patient-specific genetic profile of diseased tissue by interrogating a plurality of genomic loci in genomic DNA and/or free DNA isolated from a biological sample obtained from the patient for the presence and/or the amount of a plurality of biomarkers, wherein

(i) the plurality of genomic loci comprises at least one mutation in each of K-ras, adenomatous polyposis coli (APC), p53, and PIK3CA, and

(ii) the presence of at least one mutation at an individual locus is indicative of the presence of diseased tissue; and

monitoring the patient-specific genetic profile by interrogating the plurality of genomic loci in genomic DNA and/or free DNA isolated from a second heterogeneous biological sample for the presence and/or the amount of the plurality of biomarkers, wherein a change of the patient-specific genetic profile is indicative of the disappearance, regression, progression or recurrence of the diseased tissue in the patient.

39. The method of claim 38, wherein said first and/or second heterogeneous biological sample is serum or plasma.