Novel nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of breast cancer

Abstract

Novel markers for breast cancer that are both sensitive and accurate. These markers are overexpressed in breast cancer specifically, as opposed to normal breast tissue. The measurement of these markers, alone or in combination, in patient samples provides information that the diagnostician can correlate with a probable diagnosis of breast cancer. The markers of the present invention, alone or in combination, show a high degree of differential detection between breast cancer and non-cancerous states.

1 . An isolated polynucleotide comprising a polynucleotide having a sequence of R11723_PEA — 1_T5 (SEQ ID NO:560).  
     
     
         2 . The isolated polynucleotide of  claim 1 , comprising a node having a sequence of: R11723_PEA — 1_node — 13(SEQ ID NO:562).  
     
     
         3 . An isolated polypeptide comprising a polypeptide having a sequence of: R11723_PEA — 1_P13 (SEQ ID NO:591).  
     
     
         4 . The isolated polypeptide of  claim 3 , comprising a chimeric polypeptide encoding for R11723_PEA — 1_P13 (SEQ ID NO:591), comprising a first amino acid sequence being at least 95% homologous to MWVLGIAATFCGLFLLPGFALQIQCYQCEEFQLNNDCSSPEFIVNCTVNVQDMCQKEV MEQSA corresponding to amino acids 1-63 of Q96AC2 (SEQ ID NO:886), which also corresponds to amino acids 1-63 of R11723_PEA — 1_P13 (SEQ ID NO:591), and a second amino acid sequence being at least about 95% homologous to a polypeptide having the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) corresponding to amino acids 64-84 of R11723_PEA — 1_P13 (SEQ ID NO:591), wherein said first and second amino acid sequences are contiguous and in a sequential order.  
     
     
         4 . (canceled)  
     
     
         5 . The isolated polynucleotide of  claim 1 , comprising an amplicon according to SEQ ID NO: 975.  
     
     
         6 . A primer pair, comprising a pair of isolated oligonucleotides capable of amplifying said amplicon of  claim 5 .  
     
     
         7 . The primer pair of  claim 6 , comprising a pair of isolated oligonucleotides: SEQ NOs 973 and 974.  
     
     
         8 . An antibody capable of specifically binding to an epitope of an amino acid sequence (SEQ ID NO:591) of  claim 3 .  
     
     
         9 . The antibody of  claim 8 , wherein said amino acid sequence comprises said tail (SEQ ID NO:1026) of  claim 4 .  
     
     
         10 . The antibody of  claim 8 , wherein said antibody is capable of differentiating between a splice variant having said epitope and a corresponding known protein PSEC (SEQ ID NO:886).  
     
     
         11 . A kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant according to  claim 1 .  
     
     
         12 . The kit of  claim 11 , wherein said kit comprises a NAT-based technology.  
     
     
         13 . The kit of  claim 11 , wherein said kit further comprises at least one primer pair capable of selectively hybridizing to a nucleic acid sequence according to  claim 1 .  
     
     
         14 . The kit of  claim 11 , wherein said kit further comprises at least one oligonucleotide capable of selectively hybridizing to a nucleic acid sequence according to  claim 1 .  
     
     
         12 . (canceled)  
     
     
         13 . (canceled)  
     
     
         14 . (canceled)  
     
     
         15 . The method of  claim 26 , wherein said detecting overexpression is performed with a NAT-based technology.  
     
     
         16 . A method for detecting breast cancer, comprising detecting overexpression of a splice variant according to  claim 3 , wherein said detecting overexpression is performed with an immunoassay.  
     
     
         17 . The method of  claim 16 , wherein said immunoassay comprises an antibody according to  claim 8 .  
     
     
         18 . A biomarker capable of detecting breast cancer, comprising a nucleic acid sequence according to  claim 1  or a fragment thereof, or an amino acid sequence according to  claim 3  or a fragment thereof.  
     
     
         19 . A method for screening for breast cancer, comprising detecting breast cancer cells with a biomarker according to  claim 18 .  
     
     
         20 . A method for diagnosing breast cancer, comprising detecting breast cancer cells with a biomarker according to  claim 18 .  
     
     
         21 . A method for monitoring disease progression and/or treatment efficacy and/or relapse of breast cancer, comprising detecting breast cancer cells with a biomarker according to  claim 18 .  
     
     
         22 . A method of selecting a therapy for breast cancer, comprising detecting breast cancer cells with a biomarker according to  claim 18  and selecting a therapy according to said detection.  
     
     
         23 . The isolated polypeptide of  claim 4 , comprising a tail of R11723_PEA — 1_P13 (SEQ ID NO:591), comprising a polypeptide being at least about 95% homologous to the sequence DTKRTNTLLFEMRHFAKQLTT (SEQ ID NO:1026) in R11723_PEA — 1_P13 (SEQ ID NO:591).  
     
     
         24 . A kit for detecting breast cancer, comprising a kit detecting overexpression of a splice variant according to  claim 3 , said kit comprising an antibody according to  claim 8 .  
     
     
         25 . The kit of  claim 24 , wherein said kit further comprises at least one reagent for performing an ELISA or a Western blot.  
     
     
         26 . A method for detecting breast cancer, comprising detecting overexpression of a splice variant according to  claim 1.