Genetic products which are differentially expressed in tumors and use thereof
The invention relates to the identification of genetic products expressed in association with tumors and to coding nucleic acids for said products. The invention also relates to the therapy and diagnosis of diseases in which the genetic products are aberrantly expressed in association with tumors, proteins, polypeptides and peptides which are expressed in association with tumors and to the coding nucleic acids for said proteins, polypeptides and peptides.
1. A method of determining the tendency of a tumor to form metastases which method comprises:
(i) detection of a nucleic acid that encodes for a tumor-associated antigen, or
(ii) detection of a tumor-associated antigen,
in a biological sample comprising tumor cells isolated from a patient having a tumor,
wherein the tumor-associated antigen is encoded by the nucleic acid of SEQ ID NO: 19,
wherein the tumor is a melanoma, breast carcinoma, bronchial carcinoma, kidney carcinoma, ovarian carcinoma, or cervical carcinoma, and
wherein the method further comprises the step of determining the tendency of the tumor to form metastases, wherein the presence of the nucleic acid that encodes for the tumor-associated antigen or presence of the tumor-associated antigen in the sample is indicative of the tendency of cells of the tumor to metastasize.
2. The method of claim 1 , wherein the detecting comprises
(i) contacting the biological sample with an agent that binds specifically to the nucleic acid or the tumor-associated antigen; and
(ii) detecting the formation of a complex between the agent and the nucleic acid or the tumor-associated antigen,
wherein the agent is a polynucleotide probe that hybridizes specifically to the nucleic acid or an antibody that specifically binds to the tumor-associated antigen.
3. The method of claim 1 , wherein the level of the nucleic acid or the tumor-associated antigen is quantified by comparison to the level of the same nucleic acid or the tumor-associated antigen present in a comparable normal biological sample.
4. The method of claim 1 , wherein the nucleic acid is detected using a polynucleotide probe that hybridizes specifically to the nucleic acid.
5. The method of claim 4 , wherein the polynucleotide probe comprises a nucleotide sequence that is complementary to 6-50 contiguous nucleotides of the nucleic acid that encodes for the tumor-associated antigen.
6. The method of claim 1 , wherein the nucleic acid is detected by selectively amplifying the nucleic acid.
7. The method of claim 1 , wherein the tumor-associated antigen or a portion thereof is detected using an antibody that specifically binds thereto.
8. The method of claim 1 , wherein the nucleic acid or the tumor-associated antigen is detected and quantified in a first biological sample at a first point in time, and subsequently is detected and quantified in at least one additional biological sample taken at a later point in time, and in which the course of the disease is monitored by comparing the level of the nucleic acid or the tumor-associated antigen found in the first biological sample to the level of the nucleic acid or the tumor-associated antigen found in the at least one additional biological sample.
9. The method of claim 1 , wherein the biological sample comprises a body fluid, a tissue, or a combination thereof.
10. The method according to claim 1 , wherein the tumor-associated antigen comprises the amino acid sequence of SEQ ID NO: 22.
11. A method of determining the presence of tumor pre-stages which method comprises:
detecting co-localization of a tumor-associated antigen and F-actin or PIP 4,5 at the plasma membrane of a cell in a biological sample isolated from a patient,
wherein the tumor-associated antigen is encoded by the nucleic acid of SEQ ID NO: 19 and
wherein the method further comprises the step of determining the presence of tumor pre-stages, wherein co-localization of the tumor-associated antigen and F-actin or PIP 4,5 at the plasma membrane of the cell is indicative of the presence of tumor pre-stages.
12. The method of claim 11 , wherein the detecting comprises
(i) contacting the biological sample with an agent that binds specifically to the tumor-associated antigen; and
(ii) detecting the formation of a complex between the agent and the tumor-associated antigen,
wherein the agent is an antibody that specifically binds to the tumor-associated antigen.
13. The method of claim 2 , wherein the agent is a polynucleotide probe that hybridizes specifically to the nucleic acid.
14. The method of claim 2 , wherein the agent is an antibody that specifically binds to the tumor-associated antigen.
15. A method of determining the tendency of a tumor to form metastases which method comprises:
detecting a tumor-associated antigen in a biological sample comprising tumor cells isolated from a patient having a tumor, wherein the tumor-associated antigen is encoded by the nucleic acid of SEQ ID NO: 19,
wherein the method further comprises the step of determining the tendency of the tumor to form metastases, wherein the presence of the tumor-associated antigen in the sample is indicative of the tendency of cells of the tumor to metastasize; and
wherein the detecting comprises:
contacting the biological sample with a monoclonal antibody that binds specifically to the tumor-associated antigen, wherein the monoclonal antibody binds to an epitope within the amino acid sequence according to SEQ ID NOs: 81, 82, 103, 104, or 105; and
detecting the formation of a complex between the antibody and the tumor-associated antigen.
16. The method according to claim 15 , wherein the tumor-associated antigen comprises the amino acid sequence of SEQ ID NO: 22.
17. The method of claim 15 , wherein the tumor-associated antigen is detected and quantified in a first biological sample at a first point in time, and subsequently is detected and quantified in at least one additional biological sample taken at a later point in time, and in which the course of the disease is monitored by comparing the level of the tumor-associated antigen found in the first biological sample to the level of the tumor-associated antigen found in the at least one additional biological sample.
18. The method of claim 16 , wherein the biological sample comprises a body fluid, a tissue, or a combination thereof.
19. The method of claim 16 , wherein the monoclonal antibody binds to an epitope within the amino acid sequence according to SEQ ID NO: 81.
20. The method of claim 16 , wherein the monoclonal antibody binds to an epitope within the amino acid sequence according to SEQ ID NO: 82.
21. The method of claim 16 , wherein the monoclonal antibody binds to an epitope within the amino acid sequence according to SEQ ID NO: 103.
22. The method of claim 16 , wherein the monoclonal antibody binds to an epitope within the amino acid sequence according to SEQ ID NO: 104.
23. The method of claim 16 , wherein the monoclonal antibody binds to an epitope within the amino acid sequence according to SEQ ID NO: 105.
24. The method of claim 16 , wherein the monoclonal antibody is coupled to a diagnostic agent.