CA125 gene and its use for diagnostic and therapeutic interventions

Abstract

The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is assembled by combining five genomic exons, four very short amino terminal sequences and one extraordinarily large exon. This domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. Additionally, an amino terminal extension is present, which comprises four genomic exons. The amino acid composition of the amino terminal extension was found to be consistent with the amino acid composition of the amino terminal domain. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. More specifically, this invention is directed to a CA125 cDNA sequence which can be introduced into animal or human cells to achieve transcription or expression of the cDNA.

We claim:  
     
         1 . An isolated nucleic acid molecule encoding CA125.  
     
     
         2 . The isolated nucleic acid molecule of  claim 1  comprising the sequence of SEQ ID NO: 4.  
     
     
         3 . The isolated nucleic acid molecule of  claim 2  wherein the sequence has at least about 70% homology with SEQ ID NO: 4.  
     
     
         4 . The isolated nucleic acid molecule of  claim 2  wherein said molecule is a fragment thereof.  
     
     
         5 . An isolated nucleic acid molecule comprising the sequence shown in SEQ ID NO: 1.  
     
     
         6 . The isolated nucleic acid molecule of  claim 5  wherein the sequence has at least about 70% homology with SEQ ID NO: 1.  
     
     
         7 . The isolated nucleic acid molecule of  claim 5  wherein said molecule is a fragment thereof.  
     
     
         8 . An isolated nucleic acid molecule comprising the sequence shown in SEQ ID NO: 2.  
     
     
         9 . The isolated nucleic acid molecule of  claim 8  wherein the sequence has at least about 70% homology with SEQ ID NO: 2.  
     
     
         10 . The isolated nucleic acid molecule of  claim 8  wherein said molecule is a fragment thereof.  
     
     
         11 . An isolated nucleic acid molecule comprising the sequence shown in SEQ ID NO: 3.  
     
     
         12 . The isolated nucleic acid molecule of  claim 11  wherein the sequence has at least about 70% homology with SEQ ID NO: 3.  
     
     
         13 . The isolated nucleic acid molecule of  claim 11  wherein said molecule is a fragment thereof.  
     
     
         14 . A polypeptide with the amino acid sequence selected from the group consisting of: (a) the amino acid sequence set forth in SEQ ID NO: 5; (b) an amino acid sequence having at least 50% sequence identity to said sequence; (c) a conservative variant of an one of (a) to (b); and (d) a fragment of any one of (a) to (c).  
     
     
         15 . A purified antibody that selectively binds to an amino acid sequence of the CA125 protein: 
 (a) wherein the amino acid sequence of the CA125 protein comprises the amino acid sequence set forth in SEQ ID NO: 5;    (b) an amino acid sequence having at least 50% sequence identity to said sequence;    (c) a conservative variant of any one of (a) to (b); and    (d) a fragment of any one of (a) to (c).    
     
     
         16 . The purified antibody of  claim 15  wherein said sequence identity is at least 60%.  
     
     
         17 . The purified antibody of  claim 15  wherein said sequence identity is at least 70%.  
     
     
         18 . The purified antibody of  claim 15  wherein said sequence identity is at least 80%.  
     
     
         19 . The purified antibody of  claim 15  wherein said sequence identity is at least 90%.  
     
     
         20 . A method to make a purified fragment of the CA125 polypeptide of SEQ ID NO: 5 comprising: 
 (a) expressing a portion of the isolated nucleic acid molecule set out in SEQ ID NO: 4 to obtain a fragment of the CA125 molecule; and    (b) purifying said fragment of the CA125 molecule.