Methods for detecting and diagnosing oral cancer

• US 7,108,969 B1
• Filed: 09/10/2001
• Issued: 09/19/2006
• Est. Priority Date: 09/08/2000
• Status: Expired due to Term

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation), Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Wong, David T. W., Todd, Charles Randolph, Mahadevappa, Mamatha, Warrington, Janet A.
• Primary Examiner(s): Johannsen, Diana B.
• Application Number:
  US09/950,016
• Time in Patent Office: 1,835 Days
• Field of Search: 435/6, 435/91.2, 435/287.2
• US Class Current: 435/6.14
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Methods of monitoring the expression of genes in malignant oral cells is disclosed. Gene expression profiles are used to identify markers associated with malignant oral cells and to diagnose oral cancer.

Claims

1. A method of monitoring a gene expression profile associated with oral cancer comprising:

contacting a first array of probes with a first population of nucleic acids derived from a human subject from one or more cells obtained from malignant oral tissue;

contacting a second array of probes with a second population of nucleic acids derived from the human subject from one or more cells obtained from normal oral tissue; and

determining relative hybridization of the first array of probes to the first population of nucleic acids relative to hybridization of the second array of probes to the second population of nucleic acids, wherein at least one nucleic acid that hybridizes differently is encoded by a gene of a gene expression profile that is associated with oral cancer, wherein the gene of the gene expression profile is selected from the group consisting of p-53 responsive gene 2, beta A inhibin, human alpha-1 collagen type I gene, placental protein 11, BENE protein, neuromedin U, flavin containing monooxygenase 2, runt-related transcription factor 1, alpha 2 collagen type I, fibrillin 1, absent in melanoma 1, nonvoltage-gated 1 alpha sodium channel, protein tyrosine kinase 6 and epithelial membrane protein 1.

2. A method of expression monitoring comprising:

contacting a first array of probes with a first population of nucleic acids derived from at least one cell derived from normal oral tissue from a human subject;

contacting a second array of probes with a second population of nucleic acids derived from at least one cell derived from malignant oral tissue from the human subject; and

determining binding of the first array of probes to the nucleic acids from the first population relative to binding of the second array of probes to the nucleic acids from the second population to identify at least one probe binding to a nucleic acid that is differentially expressed between the first and second populations, wherein the nucleic acid is encoded by a gene selected from the group consisting of p-53 responsive gene 2, beta A inhibin, human alpha-1 collagen type I gene, placental protein 11, BENE protein, neuromedin U, flavin containing monooxygenase 2, runt-related transcription factor 1, alpha 2 collagen type I, fibrillin 1, absent in melanoma 1, nonvoltage-gated 1 alpha sodium channel, protein tyrosine kinase 6 and epithelial membrane protein 1.

3. A method of diagnosing a human subject with oral cancer, the method comprising:

detecting a level of expression of a marker selected from a group of markers associated with oral cancer in a test sample from the human subject; and

detecting the level of expression of the marker in a control sample from normal tissue from the human subject,

wherein the level of expression of the marker in the control sample differs from the level of expression of the marker in the test sample when the subject is afflicted with oral cancer, and wherein the marker is encoded by a gene selected from p-53 responsive gene 2, beta A inhibin, human alpha-1 collagen type I gene, placental protein 11, BENE protein, neuromedin U, flavin containing monooxygenase 2, runt-related transcription factor 1, alpha 2 collagen type I, fibrillin 1, absent in melanoma 1, nonvoltage-gated 1 alpha sodium channel, protein tyrosine kinase 6 and epithelial membrane protein 1.

4. The method of claim 3, wherein the test sample from the subject comprises cells obtained from the subject.

5. The method of claim 4, wherein the cells are obtained from oral tissue.

6. The method of claim 4, wherein the cells are obtained from blood cells.

7. The method of claim 3, wherein the levels of expression of the marker in the control sample and in the test sample are assessed by a method comprising:

contacting a first array of probes with a first population of nucleic acids derived from one or more cells from the test sample;

contacting a second array of probes with a second population of nucleic acids derived from one or more cells from the control sample; and

determining relative hybridization of the first array of probes to the first population of nucleic acids relative to hybridization of the second array of probes to the second population of nucleic acids.

8. The method of claim 7, wherein the first and second population of nucleic acids are RNA.

9. The method of claim 7, wherein the first and second population of nucleic acids are DNA.

10. The method of claim 7, wherein the first population of nucleic acids is amplified prior to contacting to the first array of probes or the second population of nucleic acids is amplified prior to contacting the second array of probes.

11. The method of claim 3, wherein the marker is a nucleic acid.

12. The method of claim 11, wherein the nucleic acid is RNA.

13. The method of claim 11, wherein the nucleic acid is DNA.

14. The method of claim 11, wherein one or more nucleic acids is amplified prior to assessing the sample.

19. The method of claim 3, wherein the control sample from the subject comprises cells obtained from the subject.

15. A method for monitoring the progression of oral cancer in a human subject, the method comprising:

detecting in a first sample obtained from the human subject at a first point in time, a level of expression of a marker selected from a group of markers associated with oral cancer;

detecting in a subsequent sample obtained from the human subject at a subsequent point in time, the level of expression of the marker, and

comparing the level of expression detected in the first and subsequent detecting samples in order to monitor the progression of oral cancer, wherein the marker is encoded by a gene selected from p-53 responsive gene 2, beta A inhibin, human alpha-1 collagen type I gene, placental protein 11, BENE protein, neuromedin U, flavin containing monooxygenase 2, runt-related transcription factor 1, alpha 2 collagen type I, fibrillin 1, absent in melanoma 1, nonvoltage-gated 1 alpha sodium channel, protein tyrosine kinase 6 and epithelial membrane protein 1.

16. The method of claim 15, wherein the first and the subsequent samples comprise cells obtained from the subject.

17. The method of claim 16, wherein the cells are obtained from oral tissue.

18. The method of claim 16, wherein the cells obtained are blood cells.