Methods for the diagnosis and treatment of lung cancer
The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell, and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.
1 . A method for detecting and diagnosing of the neoplastic condition of a lung cell, comprising detecting the presence of an overexpressed proto-oncogene selected from the group consisting of b-myb, p67, PGP9.5 and 8-oxo-dGTPase, in a lung cell sample, wherein the overexpression is indicative of the neoplastic condition of the lung cell.
2 . The method of claim 1 , wherein the proto-oncogene is b-myb.
3 . The method of claim 1 , wherein the proto-oncogene is PGP9.5.
4 . The method of claim 1 , wherein the proto-oncogene is 8-oxo-dGTPase.
5 . The method of claim 1 , wherein the proto-oncogene is p67.
6 . The method of claim 1 , wherein the presence of the overexpressed proto-oncogene is determined by detecting the quantity of mRNA transcribed from the proto-oncogene.
7 . The method of claim 2 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence TGCTGCCCTG (SEQ. ID No. 1) or its complement.
8 . The method of claim 3 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence is CAGTCTAAAA (SEQ. ID No. 2) or its complement.
9 . The method of claim 4 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence TGGCCCGACG (SEQ. ID No. 3) or its complement.
10 . The method of claim 5 , wherein the detecting is determined by probing the sample with a probe or primer comprising the sequence TAATACTTTT (SEQ ID NO. 4) or its complement.
11 . The method of claim 6 , wherein the presence of the overexpressed proto-oncogene is determined by detecting the quantity of cDNA produced from the reverse transcription of the mRNA.
12 . The method of claim 1 , wherein the presenece of the overexpressed proto-oncogene is determined by detecting the quantity of the polypeptide or protein encoded by the proto-oncogene.
13 . The method of claim 12 , wherein the lung cancer is non-small cell lung cancer.
14 . A screen for a potential therapeutic agent for the reversal of the neoplastic condition of a lung cell wherein the cell is characterized by overexpression of a proto-oncogene selected from the group consisting of b-myb, p67, PGP9.5 and 8-oxo-dGTPase comprising contacting a sample with an effective amount of a potential agent and assaying for reversal of the neoplastic condition.
15 . The screen of claim 14 , wherein the proto-oncogene is b-myb.
16 . The method of claim 14 , wherein the proto-oncogene is PGP9.5.
17 . The method of claim 14 , wherein the proto-oncogene is 8-oxo-dGTPase.
18 . The method of claim 14 , wherein the proto-oncogene is p67.
19 . A method for reversing the neoplastic condition of a lung cell, wherein the cell is characterized by overexpression of a proto-oncogene comprising contacting the cell with an agent identified by the method of claim 14 .
20 . The method of claim 19 , wherein the proto-oncogene is b-myb.
21 . The method of claim 19 , wherein the proto-oncogene is PGP9.5.
22 . The method of claim 19 , wherein the proto-oncogene is 8-oxo-dGTPase.
23 . The method of claim 19 , wherein the proto-oncogene is p67.
24 . The method of claims 19 , wherein the agent is anti-sense RNA that specifically inhibits the overexpression of the proto-oncogene.
25 . A probe or primer to detect the presence of b-myb, comprising sequence TGCTGCCCTG (SEQ. ID No. 1) or its complement.
26 . A probe or primer to detect the presence of PGP9.5, comprising sequence CAGTCTAAAA (SEQ. ID No. 2) or its complement.
27 . A probe or primer to detect the presence of 8-oxo-dGTPase, comprising sequence TGGCCCGACG (SEQ. ID No. 3) or its complement.
28 . A probe or primer to detect the presence of p67, comprising sequence TAATACTTTT (SEQ ID NO. 4) or its complement.
29 . A solid phase support comprising the probes or primers of claims through 28 , or their complements.
30 . A kit for use in a diagnostic method according to claim 1 comprising in suitable packaging:
one or more polynucleotides selected from the group consisting of b-myb, p67, PGP9.5 and 8-oxo-dGTPase immobilized on a solid support and
a reagent suitable for hybridizing a sample suspected of containing the lung cancer cell.
31 . A method for identifying a patient predisposed to developing lung cancer, comprising detecting the expression level of the b-myb proto-oncogene in a sample isolated from the patient, wherein the presence of overexpression of the b-myb proto-oncogene identifies the patient as predisposed to developing lung cancer.
32 . The method of claim 31 , further comprising detecting the expression level of a proto-oncogene of the group consisting of p77, PGP9.5 and 8-oxo-dGTPase, wherein the overexpression of at least one of the proto-oncogenes identifies the patient as predisposed to developing lung cancer.