Liver tumor marker sequences

Abstract

Polypeptides whose expression is upregulated in liver tumor cells and cells from liver preneoplastic foci relative to expression in normal liver cells are disclosed as are polynucleotides that encode the polypeptides. In humans, the polynucleotide maps to a region of chromosome 15. The overexpression has also been confirmed in human liver, breast, colon and kidney cancer cell lines. It is believed that the polypeptides are overexpressed in tumor and preneoplastic cells in general.

1 . An isolated nucleic acid comprising a polynucleotide selected from the group consisting of (1) a first nucleotide sequence that encodes a polypeptide selected from the group consisting of amino acid 22 to amino acid 439 of SEQ ID NO:2, amino acid 22 to amino acid 400 of SEQ ID NO:4, a sequence that is at least about 68% identical to amino acid 22 to amino acid 439 of SEQ ID NO:2, and a sequence that is at least about 68% identical to amino acid 22 to amino acid 400 of SEQ ID NO:4, (2) a second nucleotide sequence that is at least 80% identical to the first nucleotide sequence, and (3) a complement of the first or second nucleotide sequence.  
     
     
         2 . The isolated nucleic acid of  claim 1 , wherein the nucleic acid consists of a polynucleotide selected from the group consisting of (1) a first nucleotide sequence that encodes a polypeptide selected from the group consisting of amino acid 22 to amino acid 439 of SEQ ID NO:2, amino acid 22 to amino acid 400 of SEQ ID NO:4, a sequence that is at least about 68% identical to amino acid 22 to amino acid 439 of SEQ ID NO:2, and a sequence that is at least about 68% identical to amino acid 22 to amino acid 400 of SEQ ID NO:4, (2) a second nucleotide sequence that is at least 80% identical to the first nucleotide sequence, and (3) a complement of the first or second nucleotide sequence.  
     
     
         3 . The isolated nucleic acid of  claim 1 , wherein the nucleic acid comprises a polynucleotide selected from the group consisting of nucleotide 88 to nucleotide 1341 of SEQ ID NO:1, nucleotide 64 to nucleotide 1200 of SEQ ID NO:3, and a complement of any of the foregoing.  
     
     
         4 . A genetic construct comprising a polynucleotide of  claim 1  operably linked a heterologous transcriptional promoter.  
     
     
         5 . A host cell comprising the genetic construct of  claim 4 .  
     
     
         6 . The isolated nucleic acid of  claim 1 , wherein the nucleic acid comprises a polynucleotide selected from the group consisting of (l) a first nucleotide sequence that encodes a polypeptide selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, a sequence that is at least about 70% identical to SEQ ID NO:2, and a sequence that is at least about 70% identical to SEQ ID NO:4, (2) a second nucleotide sequence that is at least 80% identical to the first nucleotide sequence, and (3) a complement of the first or second nucleotide sequence.  
     
     
         7 . The isolated nucleic acid of  claim 6 , wherein the nucleic acid consists of a polynucleotide selected from the group consisting of (1) a first nucleotide sequence that encodes a polypeptide selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, a sequence that is at least 70% identical to SEQ ID NO:2, and a sequence that is at least 70% identical to SEQ ID NO:4, (2) a second nucleotide sequence that is at least 80% identical to the first nucleotide sequence, and (3) a complement of the first or second nucleotide sequence.  
     
     
         8 . The isolated nucleic acid of  claim 6 , wherein the nucleic acid comprises a polynucleotide selected from the group consisting of nucleotide 25 to nucleotide 1341 of SEQ ID NO:1, nucleotide 1 to nucleotide 1200 of SEQ ID NO:3, and a complement of any of the foregoing.  
     
     
         9 . A genetic construct comprising a polynucleotide of  claim 6  operably linked a heterologous transcriptional promoter.  
     
     
         10 . A host cell comprising the genetic construct of  claim 9 .  
     
     
         11 . An isolated polypeptide comprising an amino acid sequence selected from amino acid 22 to amino acid 439 of SEQ ID NO:2 and a sequence that is at least about 68% identical to amino acid 22 to amino acid 439 of SEQ ID NO:2.  
     
     
         12 . The isolated polypeptide of  claim 11  wherein polypeptide consists of an amino acid sequence selected from amino acid 22 to amino acid 439 of SEQ ID NO:2 and a sequence that is at least about 68% identical to amino acid 22 to amino acid 439 of SEQ ID NO:2.  
     
     
         13 . The isolated polypeptide of  claim 1   1 , wherein the polypeptide comprises amino acid 22 to amino acid 439 of SEQ ID NO:2.  
     
     
         14 . An isolated polypeptide comprising an amino acid sequence selected from SEQ ID NO:2 and a sequence that is at least about 70% identical to SEQ ID NO:2.  
     
     
         15 . The isolated polypeptide of  claim 14  wherein the polypeptide consists of an amino acid sequence selected from SEQ ID NO:2 and a sequence that is at least about 70% identical to SEQ ID NO:2.  
     
     
         16 . The isolated polypeptide of  claim 14 , wherein the polypeptide comprises SEQ ID NO:2.  
     
     
         17 . An antibody that specifically binds to a polypeptide consisting of an amino acid sequence encoded by the first nucleotide sequence in  claim 1 .  
     
     
         18 . An antibody that specifically binds to a polypeptide consisting of an amino acid sequence encoded by the first nucleotide sequence in  claim 6 .  
     
     
         19 . A method for identifying an agent that can modulate the expression of a polynucleotide of  claim 1 , the method comprising the steps of: 
 exposing a cell that comprises a polynucleotide of  claim 1  under the control of its native promoter;    measuring the expression of the polynucleotide in the cell; and    comparing the expression to that in a control cell that is not exposed to the test agent, wherein a higher or lower than the expression in the control cell indicates that the agent can modulate the expression of the polynucleotide.    
     
     
         20 . The method of  claim 19 , wherein the cell that comprises a polynucleotide of  claim 1  under the control of its native promoter is a cell selected from the group consisting of a liver cell, a breast cell, a kidney cell and a colon cell.  
     
     
         21 . A method for diagnosing a cancer or preneoplastic development in a tissue or organ of a human or non-human animal, the method comprising the steps of: 
 measuring the expression of a polynucleotide of  claim 1  in cells of the tissue or organ obtained from a region suspected of cancer or preneoplastic development; and    comparing the expression of the polynucleotide to a normal standard wherein a higher than normal expression indicates cancer or preneoplastic development in the tissue or organ in the suspect region.    
     
     
         22 . The method of  claim 21 , wherein the tissue or organ is liver.  
     
     
         23 . A method for identifying a human or non-human animal as a candidate for further screening for cancer or preneoplastic development in a tissue or organ, the method comprising the steps of: 
 determining the level of a polypeptide in a blood or blood-derived sample from the animal wherein the polypeptide comprises an amino acid sequence encoded by the first nucleotide sequence in  claim 1;     comparing the level to a normal range established by the same animal during a period that is tumor-free in the tissue or organ, or by a plurality of animals of the same species that are tumor-free in the tissue or organ; and    identifying the animal as a candidate for further cancer screening when the level exceeds the established normal range.    
     
     
         24 . The method of  claim 23 , wherein the tissue or organ is liver.  
     
     
         25 . A method for identifying a human or non-human animal as a candidate for further screening for cancer or preneoplastic development in a tissue or organ, the method comprising the steps of: 
 determining the level of an antibody to a polypeptide in a blood or blood-derived sample from the animal wherein the polypeptide comprises an amino acid sequence encoded by the first nucleotide sequence in  claim 1;     comparing the level to a normal range established by the same animal during a period that is tumor-free in the tissue or organ, or by a plurality of animals of the same species that are tumor-free in the tissue or organ; and    identifying the animal as a candidate for further cancer screening when the level exceeds the established normal range.    
     
     
         26 . The method of  claim 25 , wherein the tissue or organ is liver.  
     
     
         27 . A kit comprising: 
 at least one of an antibody that specifically binds to a polypeptide consisting of an amino acid sequence encoded by the first nucleotide sequence in  claim 1 , and a probe that hybridizes to the polynucleotide in  claim 1;  and    at least one control sample component for which the relative or absolute amount of the polypeptide or polynucleotide is known.    
     
     
         28 . A kit as claimed in  claim 27  wherein the control sample component is selected from the group consisting of liver cancer cells, preneoplastic liver cells, normal liver cells, breast cancer cells, normal breast cells, colon cancer cells, normal colon cells, kidney cancer cells, normal kidney cells, an extract of any of the foregoing cells, a blood sample from a human or non-human animal, and a blood-derived sample from a human or non-human animal.  
     
     
         29 . A kit as claimed in  claim 27 , wherein the control sample component is an isolated polypeptide consisting of an amino acid sequence encoded by the first nucleotide sequence in  claim 1 , or an isolated nucleic acid consisting of the polynucleotide in  claim 1 .  
     
     
         30 . A kit comprising: 
 at least one of an antibody that specifically binds to a polypeptide consisting of an amino acid sequence encoded by the first nucleotide sequence in  claim 6 , and a probe that hybridizes to the polynucleotide in  claim 6;  and    at least one control sample component for which the relative or absolute amount of the polypeptide or polynucleotide is known.    
     
     
         31 . A kit as claimed in  claim 30 , wherein the control sample component is an isolated polypeptide consisting of an amino acid sequence encoded by the first nucleotide sequence in  claim 6 , or an isolated nucleic acid consisting of the polynucleotide in  claim 6 .  
     
     
         32 . A kit as claimed in  claim 31 , wherein the isolated polypeptide is selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4, and the isolated nucleic acid is selected from the group consisting of nucleotide 25 to nucleotide 1341 of SEQ ID NO:1 and nucleotide 1 to nucleotide 1200 of SEQ ID NO:3.