Compositions, kits, and methods for identification, assessment, prevention, and therapy of cervical cancer

Abstract

The invention relates to nucleic acid molecules and proteins associated with cervical cancer including pre-malignant conditions such as dysplasia. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human cervical cancers are also provided.

1 . A method of assessing whether a patient is afflicted with cervical cancer or has a pre-malignant condition, the method comprising:
 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; and   b) determining the level of expression of the marker in a control sample,   c) comparing the level of expression of the marker in the patient sample and the control sample;   wherein a difference between the level of expression of the marker in the patient sample as compared to the level of expression of the marker in the control sample is an indication that the patient is afflicted with cervical cancer or has a pre-malignant condition.   
     
     
         2 . The method of  claim 1 , wherein the patient has CIN or SIL. 
     
     
         3 .- 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the patient sample comprises cells obtained from the patient. 
     
     
         6 . The method of  claim 5 , wherein the patient sample is a cervical smear. 
     
     
         7 . The method of  claim 5 , wherein the cells are in a fluid selected from the group consisting of a fluid collected by peritoneal rinsing, a fluid collected by uterine rinsing, a uterine fluid, a uterine exudate, a pleural fluid, a cystic fluid, and an cervical exudate. 
     
     
         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 .- 10 . (canceled) 
     
     
         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 .- 15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the level of expression of the marker in the patient sample differs from the level of expression of the marker in the control sample by a factor of at least about 2. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 1 , further comprising:
 a) determining the level of expression in the patient sample of each of a plurality of markers independently selected from the markers listed in Table 1, and   b) determining the level of expression of each of the plurality of markers in a of control sample,   c) comparing the level of expression of each of the plurality of markers in the patient sample and the control sample;   wherein a difference between the level of expression of one or more of the plurality of markers in the patient sample as compared to the level of expression of the one or more of the plurality of markers in the control sample is an indication that the patient is afflicted with cervical cancer or has a pre-malignant condition.   
     
     
         19 . The method of  claim 18 , wherein a difference between the level of expression of each of the plurality of markers in the patient sample as compared to the level of expression of each of the plurality of markers in the control sample is an indication that the patient is afflicted with cervical cancer or has a pre-malignant condition. 
     
     
         20 . The method of  claim 18 , wherein the plurality of markers comprises at least three of the markers. 
     
     
         21 . The method of  claim 18 , wherein the plurality of markers comprises at least five of the markers. 
     
     
         22 . A method for monitoring the progression of cervical cancer or a pre-malignant condition in a patient, the method comprising:
 a) detecting in a patient sample at a first point in time, the expression of a marker selected from the group consisting of the markers listed in Table 1;   b) repeating step a) at a subsequent point in time; and   c) comparing the level of expression of the marker detected in steps a) and b), thereby monitoring the progression of cervical cancer or a pre-malignant condition in the patient.   
     
     
         23 .- 24 . (canceled) 
     
     
         25 . The method of  claim 22 , wherein the sample comprises cells obtained from the patient. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 22 , wherein between the first point in time and the subsequent point in time, the patient has undergone surgery to remove a tumor. 
     
     
         28 . A method of assessing the efficacy of a test compound for inhibiting cervical 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,   wherein a lower level of expression of the marker in the first sample as compared, to the second sample is an indication that the test compound is efficacious for inhibiting cervical cancer in the patient.   
     
     
         29 .- 33 . (canceled) 
     
     
         34 . A kit for assessing whether a patient is afflicted with cervical cancer or a pre-malignant condition, the kit comprising reagents for assessing expression of a marker selected from the group consisting of the markers listed in Table 1. 
     
     
         35 .- 40 . (canceled) 
     
     
         41 . A method of inhibiting the development of cervical cancer in a subject at risk for developing cervical cancer, the method comprising inhibiting in said subject expression of a gene corresponding to a marker selected from the markers listed in Table 1. 
     
     
         42 . An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of the nucleotide sequences set forth in Tables 2 and 3. 
     
     
         43 . A vector which contains the nucleic acid molecule of  claim 42 . 
     
     
         44 . A host cell which contains the nucleic acid molecule of  claim 42 . 
     
     
         45 .- 48 . (canceled) 
     
     
         49 . An isolated polypeptide selected from the group consisting of:
 a) an isolated polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1, 7, 9, 11, 17, 19, 21, 23, 25, 27, 33, and 43; and   b) an isolated polypeptide comprising an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOs: 2, 8, 10, 20, 22, 26, 28, and 44.   
     
     
         50 . An antibody which selectively binds to the polypeptide of  claim 49 .