Compositions and methods relating to DNA mismatch repair genes

• US 20030224463A1
• Filed: 01/22/2003
• Published: 12/04/2003
• Est. Priority Date: 12/17/1993
• Status: Abandoned Application

• Current Assignee: Bronner C. Eric, Richard D. Kolodner, Robert M. Liskay, Roni J. Bollag, Sean M. Baker
• Original Assignee: Bronner C. Eric, Richard D. Kolodner, Robert M. Liskay, Roni J. Bollag, Sean M. Baker
• Inventors: Liskay, Robert M., Baker, Sean M., Bollag, Roni J., Bronner, C. Eric, Kolodner, Richard D.
• Application Number:
  US10/349,607
• Publication Number:
  US 20030224463A1
• Time in Patent Office: Days
• US Class Current: 435/7.23
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays

Abstract

Genomic sequences of human mismatch repair genes and gene products are described, as are methods of detecting mutations and/or polymorphisms in those genes. Also described are methods of diagnosing cancer susceptibility in a subject, and methods of identifying and classifying mismatch-repair-defective tumors. In particular, sequences and methods relating to human mutL homologs, hMLH1 and hPMS1 genes and gene products are provided.

Claims

1. A method of determining whether a person is susceptible to cancer comprising:

collecting a sample from the person,

contacting the sample with antibodies that bind specifically to a mutL homolog protein, and

detecting binding or lack of binding antibodies to mutL homolog protein.

2. The method of claim 1 comprising specific binding of antibodies to hMLH1 protein as shown in SEQ ID NO:

5.

3. The method of claim 1, wherein the antibodies are polyclonal.

4. The method of claim 1, wherein the antibodies are monoclonal.

5. The method of claim 1, wherein the antibodies are conjugated to a fluorescent compound.

6. A method of determining whether tumor tissue has a deficient amount of a mutL homolog protein comprising

obtaining a cross-section of a tumor specimen,

contacting the cross-section with a purified antibody that binds specifically to a mutL homolog protein, and

determining the presence or absence of antibody bound to a mutL homolog protein in the cross-section.

7. The method of claim 6, wherein the antibody is a monoclonal antibody.

8. The method of claim 6, wherein the antibody is a polyclonal antibody.

9. The method of claim 6, wherein the antibody is conjugated to a fluorescent compound.

10. The method of claim 6 further comprising

prescribing a therapy regimen based at least partially on results of the determining step.

11. The method of claim 6 further comprising

eluting unbound antibody from the cross-section.

12. The method of claim 6, wherein the antibody binds specifically to hMLH1 protein.

13. A method of manufacturing antibodies that bind specifically to a mutL homolog protein comprising

synthesizing or isolating at least a portion of a mutL homolog protein,

overexpressing the protein in bacteria,

purifying the protein,

injecting the protein into a mouse,

generating a hybridoma by fusing a lymphocyte from the mouse with a myeloma cell, and

isolating monoclonal antibodies produced by the hybridoma, wherein the antibodies bind specifically to a mutL homolog protein.

14. The method of claim 13, wherein the monoclonal antibodies bind specifically to hMLH1 protein as shown in SEQ ID NO:

5.