Bibliographic Details
| Title: |
DETECTING CYP24 EXPRESSION LEVEL AS A MARKER FOR PREDISPOSITION TO CANCER |
| Document Number: |
20120322674 |
| Publication Date: |
December 20, 2012 |
| Appl. No: |
13/443639 |
| Application Filed: |
April 10, 2012 |
| Abstract: |
This invention pertains to the discovery that an amplification of the CYP24 gene or an increase in CYP24 activity is a marker for the presence of, progression of, or predisposition to, a cancer (e.g., breast cancer). Using this information, this invention provides methods of detecting a predisposition to cancer in an animal. The methods involve (i) providing a biological sample from an animal (e.g. a human patient); (ii) detecting the level of CYP24 within the biological sample; and (iii) comparing the level of CYP24 with a level of CYP24 in a control sample taken from a normal, cancer-free tissue where an increased level of CYP24 in the biological sample compared to the level of CYP24 in the control sample indicates the presence of said cancer in said animal. |
| Inventors: |
Albertson, Donna G. (Lafayette, CA, US); Pinkel, Daniel (Walnut Creek, CA, US); Collins, Colin (San Rafael, CA, US); Gray, Joe W. (San Francisco, CA, US); Ylstra, Bauke (San Francisco, CA, US) |
| Assignees: |
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA (Oakland, CA, US) |
| Claim: |
1. A method of detecting a predisposition to cancer in an animal, said method comprising: (i) providing a biological sample from said animal; (ii) detecting the level of CYP24 within said biological sample; and (iii) comparing said level of CYP24 with a level of CYP24 in a control sample taken from a normal, cancer-free tissue; wherein an increased level of CYP24 in said biological sample compared to the level of CYP24 in said control sample indicates a predisposition to cancer in said animal. |
| Claim: |
2. The method of claim 1, wherein said level of CYP24 is detected by determining the copy number of CYP24 genes in the cells of said biological sample. |
| Claim: |
3. The method of claim 2, wherein said copy number is measured using Comparative Genomic Hybridization (CGH). |
| Claim: |
4. The method of claim 1, wherein said copy number is determined by hybridization to an array of nucleic acid probes. |
| Claim: |
5. The method of claim 3, wherein said Comparative Genomic Hybridization is performed on an array. |
| Claim: |
6. The method of claim 1, wherein said level of CYP24 is detected by measuring the level of CYP24 mRNA in said biological sample, wherein an increased level of CYP24 RNA in said sample compared to CYP24 RNA in said control sample indicates a predisposition to cancer. |
| Claim: |
7. The method of claim 6, wherein said level of CYP24 mRNA is measured in said biological sample and said control sample at the same vitamin D receptor activity or the CYP24 mRNA levels are normalized to the level of vitamin D receptor activity in the sample and control. |
| Claim: |
8. The method of claim 6, wherein said level of CYP24 mRNA is measured by hybridization to one or more probes on an array. |
| Claim: |
9. The method of claim 1, wherein said level of CYP24 is detected by measuring the level of CYP24 protein in said biological sample, wherein an increased level of CYP24 protein in said sample as compared to CYP24 protein in said control sample indicates a predisposition to cancer. |
| Claim: |
10. The method of claim 9, wherein the level of CYP24 protein is measured in the biological sample and the control sample at the same vitamin D receptor activity or the protein levels are normalized to the level of vitamin D receptor activity in the sample and control. |
| Claim: |
11. The method of claim 1, wherein said level of CYP24 is detected by measuring the level of 25-hydroxyvitamin D3 24-hydroxylase enzyme activity in said biological sample, wherein an increased level of 25-hydroxyvitamin D3 24-hydroxylase enzyme activity in said sample as compared to 25-hydroxyvitamin D3 24-hydroxylase enzyme activity in said control sample indicates a predisposition to cancer. |
| Claim: |
12. The method of claim 11, wherein said level of 25-hydroxyvitamin D3 24-hydroxylase activity is measured in said biological sample and said control sample at the same vitamin D receptor activity or the activity levels are normalized to the level of vitamin D receptor activity in the sample and control. |
| Claim: |
13. The method of claim 1, wherein said animal is a mammal selected from the group consisting of humans, non-human primates, canines, felines, murines, bovines, equines, porcines, and lagomorphs. |
| Claim: |
14. The method of claim 1, wherein said biological sample is selected from the group consisting of excised tissue, whole blood, serum, plasma, buccal scrape, saliva, cerebrospinal fluid, and urine. |
| Claim: |
15. The method of claim 1, wherein the difference between said increased level of CYP24 in said biological sample and the level of CYP24 in said control sample is a statistically significant difference. |
| Claim: |
16. The method of claim 1, wherein said increased level of CYP24 in said biological sample is at least about 2-fold greater than the level of CYP24 in said control sample. |
| Claim: |
17. The method of claim 1, wherein said increased level of CYP24 in said biological sample is at least about 4-fold greater than said level of CYP24 in said control sample. |
| Claim: |
18. A method of estimating the survival expectancy of an animal with cancer, said method comprising: (i) providing a biological sample from said animal; (ii) detecting the level of CYP24 within said biological sample; and (iii) comparing said level of CYP24 with the level of CYP24 in a control sample taken from a normal, cancer-free tissue; wherein an increased level of CYP24 in said biological sample compared to the level of CYP24 in said control sample indicates a reduced survival expectancy in said animal compared to in an animal with cancer that has a normal level of CYP24. |
| Claim: |
19-50. (canceled) |
| Claim: |
51. A method of screening a test agent for the ability to inhibit proliferation of a CYP24-expressing cell, said method comprising: (i) contacting said CYP24-expressing cell with said test agent; and (ii) detecting the level of CYP24 activity; wherein a decreased level of CYP24 activity as compared to the level of CYP24 activity in a cell not contacted with said agent indicates that said agent inhibits proliferation of said cell. |
| Claim: |
52-63. (canceled) |
| Claim: |
64. A method of decreasing the proliferation of a cell with an elevated level of CYP24, said method comprising reducing the level of CYP24 activity in said cell using an inhibitor of CYP24. |
| Claim: |
65-70. (canceled) |
| Current U.S. Class: |
506/9 |
| Current International Class: |
40; 12; 12; 40; 12; 01 |
| Accession Number: |
edspap.20120322674 |
| Database: |
USPTO Patent Applications |
