Nucleic acid molecules and proteins for the identification, assessment, prevention, and therapy of ovarian cancer

Abstract

The invention relates to newly discovered nucleic acid molecules and proteins associated with ovarian cancer. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human ovarian cancers are provided.

1 . A method of assessing whether a patient is afflicted with ovarian cancer, the method comprising the steps of:
 a) determining the level of expression of a marker in a patient sample, wherein the marker is selected from the group consisting of the markers listed in Table 1;   b) determining the level of expression of the marker in a sample from a control subject having no ovarian cancer or no ovarian tumor; and   c) comparing the level of expression of the marker in the patient sample and in the sample from the control subject   wherein a significant difference between the level of expression of the marker in the patient sample and the sample from the control subject is an indication that the patient is afflicted with breast cancer.   
     
     
         2 . The method of  claim 1 , wherein the level of expression from the control subject is determined from ovarian cells from said patient which appear to be non-cancerous. 
     
     
         3 . The method of  claim 1 , wherein the level of expression from the control subject is predetermined using an average of the levels of expression from a population of subjects having no ovarian cancer. 
     
     
         4 . The method of  claim 1 , wherein the marker corresponds to a secreted protein. 
     
     
         5 . The method of  claim 1 , wherein the marker corresponds to a transcribed polynucleotide or portion thereof, wherein the polynucleotide comprises the marker. 
     
     
         6 . The method of  claim 1 , wherein the sample comprises cells obtained from the patient. 
     
     
         7 . The method of  claim 6 , wherein the cells are in a fluid selected from the group consisting of blood fluids, lymph, ascites, gynecological fluids, cystic fluid, urine, and fluids collected by peritoneal rinsing. 
     
     
         8 . The method of  claim 1 , wherein the level of expression of the marker in the sample is assessed by detecting the presence in the sample of a protein corresponding to the marker. 
     
     
         9 . The method of  claim 8 , wherein the presence of the protein is detected using a reagent which specifically binds with the protein. 
     
     
         10 . The method of  claim 9 , wherein the reagent is selected from the group consisting of an antibody, an antibody derivative, and an antibody fragment. 
     
     
         11 . The method of  claim 1 , wherein the level of expression of the marker in the sample is assessed by detecting the presence in the sample of a transcribed polynucleotide or portion thereof, wherein the transcribed polynucleotide comprises the marker. 
     
     
         12 . The method of  claim 11 , wherein the transcribed polynucleotide is a mRNA or a cDNA. 
     
     
         13 . The method of  claim 11 , wherein the step of detecting further comprises amplifying the transcribed polynucleotide. 
     
     
         14 . The method of  claim 1 , wherein the level of expression of the marker in the sample is assessed by detecting the presence in the sample of a transcribed polynucleotide which anneals with the marker or anneals with a portion of a polynucleotide wherein the polynucleotide comprises the marker, under stringent hybridization conditions. 
     
     
         15 . The method of  claim 1 , wherein the level of expression of the marker in the sample differs from the normal level of expression of the marker in a patient not afflicted with ovarian cancer by a factor of at least about 2. 
     
     
         16 . The method of  claim 1 , wherein the level of expression of the marker in the sample differs from the normal level of expression of the marker in a patient not afflicted with ovarian cancer by a factor of at least about 5. 
     
     
         17 . A method of assessing whether a patient is afflicted with ovarian cancer, the method comprising the steps of:
 a) determining the level of expression in the sample of each of a plurality of markers independently selected from the markers listed in Table 1;   b) determining the level of expression of each of the plurality of markers in a sample from a control subject having no ovarian cancer; and   c) comparing the level of expression of the marker in the patient sample and in the sample from the control subject;   wherein the level of expression of more than one of the markers is significantly altered, relative to the corresponding control levels of expression of the markers, is an indication that the patient is afflicted with ovarian cancer.   
     
     
         18 . The method of  claim 17 , wherein the levels of expression from a control subject are determined from ovarian cells from said patient which appear to be non-cancerous. 
     
     
         19 . The method of  claim 17 , wherein the levels of expression from a control subject are predetermined using an average of the levels of expression from a population of subjects having no ovarian cancer. 
     
     
         20 . The method of  claim 17 , wherein the plurality comprises at least three of the markers. 
     
     
         21 . The method of  claim 17 , wherein the plurality comprises at least five of the markers. 
     
     
         22 . A method for determining whether a patient has ovarian cancer that has metastasized or is likely to metastasize, the method comprising comparing:
 a) the level of expression of a marker listed in Table 1 in a sample from the patient, and   b) the level of expression of the marker in a sample from a control subject having a non-metastasized ovarian cancer or no ovarian cancer,   c) wherein, a significantly higher level of expression in the patient sample as compared to the level in the sample from the control subject is an indication that the ovarian cancer has metastasized or is likely to metastasize.   
     
     
         23 . A method of assessing the efficacy of a test compound for inhibiting ovarian cancer in a patient, the method comprising comparing:
 a) expression of a marker in a first sample obtained from the patient and exposed to the test compound, wherein the marker is selected from the group consisting of the markers listed in Table 1, and   b) expression of the marker in a second sample obtained from the patient, wherein the sample is not exposed to the test compound,   c) wherein a significantly lower level of expression of the marker in the first sample, relative to the second sample, is an indication that the test compound is efficacious for inhibiting ovarian cancer in the patient.   
     
     
         24 . The method of  claim 23 , wherein the first and second samples are portions of a single sample obtained from the patient. 
     
     
         25 . The method of  claim 23 , wherein the first and second samples are portions of pooled samples obtained from the patient. 
     
     
         26 . A method of assessing the efficacy of a therapy for inhibiting ovarian cancer in a patient, the method comprising comparing:
 a) expression of a marker in a first sample obtained from the patient prior to administering at least a portion of the therapy to the patient, wherein the marker is selected from the group consisting of the markers listed in Table 1, and   b) expression of the marker in a second sample obtained from the patient subsequent to administering the portion of the therapy,   c) wherein a significantly lower level of expression of the marker in the second sample, relative to the first sample, is an indication that the therapy is efficacious for inhibiting ovarian cancer in the patient.   
     
     
         27 . A method of selecting a composition for inhibiting ovarian cancer in a patient, the method comprising:
 a) obtaining a sample comprising cancer cells from the patient;   b) separately exposing aliquots of the sample in the presence of a plurality of test compositions;   c) comparing expression of a marker in each of the aliquots, wherein the marker is selected from the group consisting of the markers listed in Table 1; and   d) selecting at least one of the test compositions which induces a lower level of expression of the marker in the aliquot containing that test composition, relative to the other test compositions.   
     
     
         28 . A method of inhibiting ovarian cancer in a patient, the method comprising:
 a) obtaining a sample comprising cancer cells from the patient;   b) separately maintaining aliquots of the sample in the presence of a plurality of test compositions;   c) comparing expression of a marker in each of the aliquots, wherein the marker is selected from the group consisting of the markers listed in Table 1; and administering to the patient at least one of the test compositions which induces a lower level of expression of the marker in the aliquot containing that test composition, relative to the other test compositions.   
     
     
         29 . A method for assessing the ovarian cell carcinogenic potential of a test composition, the method comprising;
 a) maintaining separate aliquots of ovarian cancer cells in the presence and absence of the test composition; and   b) comparing expression of a marker in each of the aliquots, wherein the marker is selected from the group consisting of the markers listed in Table 1,   
       wherein a significantly enhanced level of expression of the marker in the aliquot maintained in the presence of the test composition, is an indication that the test composition possesses human ovarian cell carcinogenic potential. 
     
     
         30 . A kit for assessing whether a patient is afflicted with ovarian cancer, the kit comprising reagents for assessing expression of a plurality of markers selected from the group consisting of the markers listed in Table 1. 
     
     
         31 . A kit for assessing the presence of ovarian cancer cells, the kit comprising a plurality of nucleic acid probes wherein the probes specifically bind with transcribed polynucleotides corresponding to a plurality of markers selected from the group consisting of the markers listed in Table 1. 
     
     
         32 . A kit for assessing the presence of ovarian cancer cells, the kit comprising a plurality of antibodies, wherein the antibodies specifically bind with proteins corresponding to a plurality of markers selected from the group consisting of the markers listed in Table 1. 
     
     
         33 . A kit for assessing the suitability of each of a plurality of compounds for inhibiting ovarian cancer in a patient, the kit comprising: a plurality of compounds; and a reagent for assessing expression of a marker selected from the group consisting of the markers listed in Table 1. 
     
     
         34 . A method of inhibiting ovarian cancer in a patient at risk for developing ovarian cancer, the method comprising inhibiting expression of a gene corresponding to a marker selected from the markers listed in Table 1. 
     
     
         35 . An isolated nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 7, SEQ ID NO:9, SEQ ID NO:17, SEQ ID NO:31, SEQ ID NO:39 or SEQ ID NO:41. 
     
     
         36 . An isolated polypeptide comprising the amino acid sequence of SEQ ID NO:10, SEQ ID NO:32, SEQ ID NO:40 or SEQ ID NO:42. 
     
     
         37 . An antibody which selectively binds to the polypeptide of  claim 36 .