Claims
- 1. A method of determining an expression pattern of a cell sample independent of the proportion of submucosal, smooth muscle, or connective tissue cells present, comprising:
determining expression of one or more genes in a sample comprising cells, wherein the one or more genes excludes genes which are expressed in the submucosal, smooth muscle, or connective tissue, whereby a pattern of expression is formed for the sample which is independent of the proportion of submucosal, smooth muscle, or connective tissue cells in the sample.
- 2. The method of claim 1 wherein the sample comprises epithelial or carcinoma cells.
- 3. The method of claim 2 wherein the sample comprises urothelial or bladder cancer cells.
- 4. A method of determining an expression pattern of a cell sample, comprising:
determining expression of one or more genes in a sample comprising cells, whereby a first pattern of expression is formed for the sample; removing expression of genes which are expressed in submucosal, smooth muscle, or connective tissue cells from the first pattern of expression, whereby a second pattern of expression is formed, wherein the second pattern is independent of the proportion of submucosal, smooth muscle, or connective tissue cells in the sample.
- 5. The method of claim 4 wherein the cell sample is an epithelium or carcinoma sample.
- 6. The method of claim 5 wherein the cell sample is a urothelium or bladder cancer sample.
- 7. A method for determining an expression pattern of a urothelium or bladder cancer cell, comprising:
determining expression of one or more genes in a sample comprising urothelium or bladder cancer cells, whereby a first pattern of expression is formed; subtracting from the first pattern of expression a second pattern of expression, wherein the second pattern was formed using the one or more genes and a sample comprising predominantly submucosal, smooth muscle, or connective tissue cells, said step of subtracting forming a third pattern of expression which reflects expression of the urothelium or bladder cancer cells independent of the proportion of submucosal, smooth muscle, or connective tissue cells present in the sample.
- 8. A method of detecting an invasive tumor in a patient, comprising:
detecting in a sample of a body fluid a marker which is more prevalent in submucosal, smooth muscle, or connective tissue than in the body fluid, wherein the marker is an mRNA or protein expression product of a gene, wherein an increased amount of the marker in the body fluid indicates a tumor which has become invasive in the patient.
- 9. The method of claim 8 wherein the body fluid is selected from the group consisting of blood, plasma, serum, urine, ascites fluid, pleural fluid, spinal fluid, sputum, and mucous secretions.
- 10. The method of claim 8 wherein the marker is a protein characteristic of submucosal, smooth muscle, or connective tissue, but not found in the body fluid.
- 11. A method to diagnose a bladder cancer comprising:
determining a first pattern of expression of one or more genes in a bladder tissue sample suspected of being neoplastic; comparing the first pattern of expression to a second and third reference pattern of expression, wherein the second pattern is of the one or more genes in normal urothelium and the third pattern is of the one or more genes in bladder cancer, wherein a first pattern of expression which is more similar to the third pattern than the second indicates neoplasia of the bladder tissue sample.
- 12. A method to predict outcome or prescribe treatment of a bladder tumor, comprising:
determining a first pattern of expression of one or more genes in a bladder tumor sample; comparing the first pattern to one or more reference patterns of expression determined for bladder tumors at grades I to IV; determining which of the reference patterns shares maximum similarity with the first pattern, wherein the outcome or treatment appropriate for the grade of tumor of the reference pattern with the maximum similarity is assigned to the bladder tumor sample.
- 13. A method to determine grade of a bladder tumor, comprising:
determining a first pattern of expression of one or more genes in a bladder tumor sample; comparing the first pattern to one or more reference patterns of expression determined for bladder tumors at grades I to IV; determining which of the reference patterns shares maximum similarity with the first pattern, wherein the grade of the reference pattern with the maximum similarity is assigned to the bladder tumor sample.
- 14. A method to determine stage of a bladder tumor, comprising:
determining a first pattern of expression of one or more genes in a bladder tumor sample; comparing the first pattern to one or more stage-specific reference patterns; determining which of the stage-specific reference patterns shares maximum similarity with the first pattern, wherein the stage of the reference pattern with the maximum similarity is assigned to the bladder tumor sample.
- 15. The method of claim 14 wherein the pattern of expression of the bladder tumor sample and the reference patterns comprise data on the expression of one or more genes selected from the group consisting of TCC-related genes, bladder papilloma-related genes, and invasive TCC-related genes.
- 16. A method of identifying a tissue sample as urothelial, comprising:
determining a first pattern of expression of one or more genes in a tissue sample; comparing the first pattern of expression to a second pattern of expression obtained from normal urothelial cells; wherein similarity between the first and second patterns identifies the tissue sample as urothelial in its origin.
- 17. The method of claim 16 further comprising the step of:
comparing the first pattern to one or more third patterns of expression obtained from other cell types, wherein differences between the first and third patterns confirms the suggestion that the tissue sample is urothelial in origin.
- 18. A method to identify a set of genes useful for diagnosing, predicting outcome, or prescribing treatment of a bladder cancer comprising:
determining a first pattern of expression of one or more genes in a first bladder tissue sample; determining a second pattern of expression of the one or more genes in a second bladder tissue sample, wherein the first bladder tissue sample is a normal urothelium sample or an earlier stage or lower grade of bladder tumor than the second bladder tissue sample; comparing the first pattern of expression to the second pattern of expression to identify a first set of genes whose expression is increased or decreased in the second bladder tissue sample relative to the first bladder tissue sample; removing from the first set of genes those genes which are expressed in submucosal, smooth muscle or connective tissue to produce a second set of genes, wherein measurement of expression of the second set of genes can be used for diagnosing, predicting outcome, or prescribing treatment of a bladder cancer.
- 19. A method of determining an expression pattern of a bladder tissue sample independent of the proportion of submucosal, smooth muscle, or connective tissue cells present, comprising:
isolating a single-cell suspension of disaggregated bladder tumor cells from a bladder tissue sample comprising bladder cells, and cells of one or more of a cell type selected from the group consisting of submucosal cells, smooth muscle cells, or connective tissue cells; determining expression of one or more genes in the single-cell suspension, whereby a pattern of expression is formed for the sample which is independent of the proportion of submucosal, smooth muscle, or connective tissue cells in the bladder tissue sample.
- 20. The method of any of claims 1-19 wherein expression of a gene is determined by assaying for an mRNA transcribed from the gene or a protein translated from an mRNA transcribed from the gene.
- 21. The method of any of claims 1-19 wherein expression of a plurality of genes is determined.
- 22. A method of screening for candidate therapeutic agents for treating bladder cancer, comprising the steps of:
contacting bladder tumor cells with a test compound; determining gene expression of one or more genes in the bladder tumor cells which have been contacted with the test compound, wherein expression of the one or more genes changes during the development of a bladder cancer; identifying a test compound as a candidate therapeutic agent if it causes gene expression of at least one of the one or more genes to change to a level which is characteristic of an earlier stage of cancer progression.
- 23. A method of categorizing a tumor, comprising the steps of:
mixing cells of a plurality of tumors, wherein the tumors are of a single type and of a similar stage or grade to form a pool; determining expression of one or more genes in the pool; comparing expression of the one or more genes in the pool to expression in a test sample derived from a tumor, wherein similarities between the test sample expression and the pool expression permit categorization of the tumor.
- 24. A method of categorizing a tumor, comprising the steps of:
mixing one or more gene products from cells of a plurality of tumors, wherein the tumors are of a single type and of a similar stage or grade to form a pool, wherein the gene product is mRNA or protein; determining expression of one or more genes in the pool by assaying the gene product in the pool; comparing expression of the one or more genes in the pool to expression in a test sample derived from a tumor, wherein similarities between the test sample expression and the pool expression permit categorization of the tumor.
- 25. A method of categorizing a tumor, comprising the steps of:
determining expression of one or more genes in a plurality of tumors, wherein the tumors are of a single type and of a similar stage or grade; combining data determined for the expression of the one or more genes to form a data pool; comparing expression of the one or more genes in the data pool to expression in a test sample derived from a tumor, wherein similarities between the test sample expression and the data pool permit categorization of the tumor.
- 26. The method of claim 23, 24, or 25 wherein the tumors are bladder tumors.
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Application No. 60/121,124, filed Feb. 22, 1999, which is hereby incorporated by reference in its entirety.
Divisions (1)
|
Number |
Date |
Country |
Parent |
09510643 |
Feb 2000 |
US |
Child |
09951968 |
Sep 2001 |
US |