Method for the analysis of differential expression in colorectal cancer

• US 20080286801A1
• Filed: 06/18/2008
• Published: 11/20/2008
• Est. Priority Date: 12/21/2005
• Status: Abandoned Application

• Current Assignee: Oryzon Genomics, S.A.
• Original Assignee: Oryzon Genomics, S.A.
• Inventors: Arjol, Carlos Buesa, Navarro, Simo Schwartz, Del Corro, Diego Arango
• Application Number:
  US12/214,522
• Publication Number:
  US 20080286801A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 33/57419 of colon

Abstract

A method for the analysis of differential expression in colorectal cancer based on the variation in the expression levels of genes encoding for proteins forming part of the condensin complex or associated proteins that occurs in patients with the disease and that can be used as markers for the diagnosis of the cancers, as well as for the prevention and treatment thereof.

Claims

1. A method for diagnosing colorectal cancer, said method comprising determining the level of one or more biomarkers in a sample, wherein said one or more biomarkers corresponds to a member of the condensin complexes or a protein associated with the protein complex, wherein an alteration in the level of the one or more biomarkers as compared to control indicates colorectal cancer or pre-malignant colorectal cancer state.

2. The method of claim 1, wherein said one or more biomarkers are chosen from a nucleic acid, a DNA, a RNA, and a protein.

3. The method of claim 1, wherein said one or more biomarkers are selected from the group consisting of hCap-E, hCap-C, hCap-D2, hCap-D3, hCap-G, hCap-G2, hCap-H, hCap-H2, and KIF4A.

4. The method of claim 1, wherein the alteration in the level of one or more biomarkers results in an increase in the level of the mRNA.

5. The method of claim 1, wherein the alteration in the level of one or more biomarkers results in an increase in the level of the protein.

6. The method of claim 1, wherein the sample is isolated from cells obtained by biopsy or any other method of extraction.

7. The method of claim 1, wherein the determining the level comprises analyzing the sample for the level of DNA or RNA.

8. The method of claim 1, wherein said determining the level is carried out by (1) PCR amplification, SDA amplification, or any other method of nucleic acid amplification, (2) using a nucleic acid microarray, (3) gel electrophoresis, (4) transfer to a membrane and hybridization with a specific probe, and (5) diagnostic imaging.

9. The method of claim 1, wherein the determining the level comprises analyzing the sample for the level of the protein.

10. The method of claim 1, wherein the analysis is carried out by (1) incubation with a specific antibody, (2) Western blot, (3) immunohistochemistry, (4) gel electrophoresis, (5) microarray, (6) ELISA, and (7) diagnostic imaging.

11. The method of claim 1, wherein the variation in the expression levels of the gene or genes is used to predict the progression of the colorectal cancer or of a premalignant condition thereof, for predicting the risk of recurrence, and/or determining the type of therapy.

14. The method of claim 1, wherein said biomarker corresponds to hCap-E nucleic acid or protein.

15. The method of claim 1, wherein said biomarker corresponds to hCap-C nucleic acid or protein.

16. The method of claim 1, wherein said biomarker corresponds to hCap-D2 nucleic acid or protein.

17. The method of claim 1, wherein said biomarker corresponds to hCap-D3 nucleic acid or protein.

18. The method of claim 1, wherein said biomarker corresponds to hCap-G nucleic acid or protein.

19. The method of claim 1, wherein said biomarker corresponds to hCap-G2 nucleic acid or protein.

20. The method of claim 1, wherein said biomarker corresponds to hCap-H nucleic acid or protein.

21. The method of claim 1, wherein said biomarker corresponds to hCap-H2 nucleic acid or protein.

22. The method of claim 1, wherein said biomarker corresponds to KIF4A nucleic acid or protein.

12. A kit for the diagnosis, prognosis, and/or prediction of recurrence of colorectal cancer, said kit comprising reagents and additives for determining the variation in the one or more biomarkers corresponding to proteins that are part of condensin complex or are associated with the condensin complex.

13. The kit of claim 12, wherein said one or more biomarkers corresponding to the condensin complex or are associated with the condensin complex are chosen from hCap-E, hCap-C, hCap-D2, hCap-D3, hCap-G, hCap-G2, hCap-H, hCap-H2, and KIF4A.

23. A method for screening for compounds with anti-colorectal cancer activity, said method comprising contacting a cell with a test compound and determining if said compound either reduces the level of expression of one or more genes that encode a component of the condensin complex or a protein associated with the condensin complex or alters the biological function of the condensin complex.

24. The method of claim 23, wherein the biological function of the condensin complex is the ability to mediate repair of DNA damage.

25. The method of claim 23, wherein the biological function of the condensin complex is the ability to mediate cell cycle control.