Method and Nucleic Acids for the Improved Treatment of Breast Cell Proliferative Disorders

Abstract

The present invention relates to modified and genomic sequences, to oligonucleotides and/or PNA-oligomers for detecting the cytosine methylation state of genomic DNA, as well as to a method for predicting the response of a subject with a cell proliferative disorder of the breast tissues, to endocrine treatment.

1 . An isolated nucleic acid molecule consisting essentially of a sequence at least 18 bases in length according to one of the sequences taken from the group consisting of SEQ ID NOs: 411, 412, 515, 516, 685, 686, 789, and 790, and sequences complementary thereto. 
     
     
         2 . An isolated oligomer selected from an oligonucleotide or peptide nucleic acid (PNA)-oligomer, said oligomer consisting essentially of at least one base sequence having a length of at least 10 nucleotides which hybridises to or is identical to one of the nucleic acid sequences according to SEQ ID NO: 411, 412, 515, 516, 685, 686, 789, and 790. 
     
     
         3 . The isolated oligomer of  claim 2 , wherein the base sequence includes at least one CpG dinucleotide. 
     
     
         4 . A plurality of oligomers, comprising at least two oligomers of  claim 2 . 
     
     
         5 . A plurality of oligomers, comprising at least two oligomers of  claim 3 . 
     
     
         6 . A plurality of oligonucleotides comprising oligomers of  claim 2 , characterised in that at least one oligonucleotide is bound to a solid phase. 
     
     
         7 . A plurality of oligonucleotides comprising oligomers of  claim 3 , characterised in that at least one oligonucleotide is bound to a solid phase. 
     
     
         8 . A plurality of oligonucleotides comprising oligomers of  claim 4 , characterised in that at least one oligonucleotide is bound to a solid phase. 
     
     
         9 . A plurality of oligonucleotides comprising oligomers of  claim 5 , characterised in that at least one oligonucleotide is bound to a solid phase. 
     
     
         10 . A plurality of at least two oligonucleotides of  claim 2 , which is used as primer oligonucleotides for the amplification of nucleic acid sequences comprising one of SEQ ID NO: 411, 412, 515, 516, 685, 686, 789, and 790, and sequences complementary thereto. 
     
     
         11 . A plurality of at least two oligonucleotides of  claim 3 , which is used as primer oligonucleotides for the amplification of nucleic acid sequences comprising one of SEQ ID NO: 411, 412, 515, 516, 685, 686, 789, and 790, and sequences complementary thereto. 
     
     
         12 . A kit comprising a bisulfite reagent and a plurality of oligonucleotides and/or PNA-oligomers according to  claim 2 . 
     
     
         13 . A kit comprising a bisulfite reagent and a plurality of oligonucleotides and/or PNA-oligomers according to  claim 3 . 
     
     
         14 . A kit according to  claim 12 , further comprising reagents for performing a methylation assay from the group consisting of MS-SNuPE, MSP, Methyl light, Heavy Methyl, nucleic acid sequencing and combinations thereof. 
     
     
         15 . A kit according to  claim 13 , further comprising reagents for performing a methylation assay from the group consisting of MS-SNuPE, MSP, Methyl light, Heavy Methyl, nucleic acid sequencing and combinations thereof. 
     
     
         16 . A method for the treatment, characterisation, classification and/or differentiation of breast cell proliferative disorders comprising contacting a nucleic acid sample from a subject with an oligonucleotide or PNA-oligomer according to  claim 2 . 
     
     
         17 . A method for the treatment, characterisation, classification and/or differentiation of breast cell proliferative disorders comprising contacting a nucleic acid sample from a subject with an oligonucleotide or PNA-oligomer according to  claim 3 .