Detection of copy number changes in colon cancer

• US 6,326,148 B1
• Filed: 07/12/1999
• Issued: 12/04/2001
• Est. Priority Date: 07/12/1999
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Pauletti, Giovanni E., Slamon, Dennis J.
• Primary Examiner(s): Arthur, Lisa B.
• Assistant Examiner(s): GOLDBERG, JEANINE ANNE
• Application Number:
  US09/351,763
• Time in Patent Office: 876 Days
• Field of Search: 435/6
• US Class Current: 435/6.18
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism

Abstract

The present invention provides methods of screening for colon carcinoma cells in a sample. The methods comprise providing a nucleic acid sample from a premalignant lesion in colorectal tissue from a human patient and contacting the sample with a nucleic acid probe that selectively hybridizes to a chromosomal region at 20q.

Claims

1. A method of screening for colon carcinoma precursor cells in a sample by determining the presence of increased copy number of chromosome 20q, the method comprising:

providing a nucleic acid sample from a premalignant lesion in colorectal tissue from a human patient;

contacting the sample with a nucleic acid probe that selectively hybridizes to a chromosomal region on 20q; and

detecting the formation of a hybridization complex, whereby the presence of increased copy number on 20q indicates the presence of colon cancer precursor cells.

2. The method of claim 1, wherein the chromosomal region is 20q13.2.

3. The method of claim 2, wherein the probe selectively hybridizes to ZNF217.

4. The method of claim 1, wherein the nucleic acid sample is a metaphase spread or an interphase nucleus.

5. The method of claim 1, wherein the probe is labeled.

6. The method of claim 4, wherein the label is a fluorescent label.

7. The method of claim 5, wherein the label is a direct label.

8. The method of claim 5, further comprising contacting the sample with a second probe that selectively hybridizes to a second chromosomal region.

9. The method of claim 7, wherein the second probe is labeled with a fluorescent label distinguishable from the label on the probe that selectively hybridizes to a chromosomal region on 20q.

10. The method of claim 1, wherein the premalignant tissue is an adenomatous polyp.

11. The method of claim 1, wherein the premalignant tissue shows high grade dysplasia.

12. The method of claim 1, further comprising the step of blocking the hybridization capacity of repetitive sequences in the probe.

13. The method of claim 12, wherein unlabeled blocking nucleic acids comprising repetitive sequences are contacted with the sample.

14. The method of claim 12, wherein the unlabeled blocking nucleic acids are Cot-1 DNA.

15. The method of claim 1, wherein probe is bound to a solid substrate.

16. The method of claim 15, wherein the probe is a member of an array.

17. The method of claim 1, wherein the nucleic acid sample is from archived material.

18. The method of claim 1, further comprising selecting a therapeutic treatment based on the determined presence of increased copy number at 20q.

19. A method of screening for colon carcinoma precursor cells in a sample by determining the presence of increased copy number of chromosome 20q13.2, the method comprising:

providing a nucleic acid sample comprising a metaphase spread or an interphase nucleus from a premalignant lesion in colorectal tissue from a human patient;

contacting the sample with a fluorescently labeled nucleic acid probe that selectively hybridizes to a chromosomal region at 20q13.2 and

detecting the formation of a hybridization complex, whereby the presence of increased copy number at 20q13.2 indicates the presence of colon carcinoma precursor cells.

20. The method of claim 19, further comprising contacting the sample with a second probe that selectively hybridizes to a second chromosomal region.

21. The method of claim 20, wherein the second chromosomal region is a centromere.

22. The method of claim 20, wherein the second probe is labeled with a fluorescent label distinguishable from the label on the probe that selectively hybridizes to a chromosomal region at 20q13.2.

23. The method of claim 19, wherein the premalignant tissue is an adenomatous polyp.

24. The method of claim 19, wherein the premalignant tissue shows high grade dysplasia.

25. The method of claim 19, wherein the probe selectively hybridizes to ZNF217.