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OwnerCathy Lofton-Day, Andrew Sledziewski +4inventors
InventorsCathy Lofton-Day, Andrew Sledziewski, Jeff Thomas, Robert Day, Lori Tonnes-Priddy, Karen Cardon
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Various aspects of the present invention provide novel diagnostic and prognostic methods for detecting, or for detecting and differentiating between or among colorectal cell proliferative disorders. Preferably, said colorectal cell proliferative disorders are selected from the group consisting of colorectal carcinoma, colon adenomas, and colon polyps. The inventive methods are based on analysis of differential CpG dinucleotide methylation of genomic DNA between or among normal and disease states. Additional embodiments provide nucleic acids and oligomers (including oligonucleotides and peptide nucleic acid (PNA)-oligomers), nucleic acid arrays and kits useful for practicing said methods, and in otherwise detecting, or detecting and differentiating between or among colorectal cell proliferative disorders.
A method for detecting, or detecting and distinguishing between or among colorectal cell proliferative disorders, comprising contacting genomic DNA of a biological sample obtained from the subject with at least one reagent, or series of reagents that distinguishes between methylated and non-methylated CpG dinucleotides within a target sequence of the genomic DNA, wherein the target sequence comprises a sequence of at least 18 contiguous nucleotides of a sequence selected from the group consisting of SEQ ID NOS:1-39.
A nucleic acid comprising a sequence of at least 18 contiguous nucleotides of a treated genomic DNA sequence selected from the group consisting of SEQ ID NOS:40-195, and sequences complementary thereto, wherein the contiguous sequence comprises at least one CpG, TpA, or CpA dinucleotide, and wherein the treatment is suitable to convert at least one unmethylated cytosine base of the genomic DNA sequence initially to uracil or another base that is detectably dissimilar to cytosine in terms of hybridization.
An oligomer or peptide nucleic acid (PNA)-oligomer, said oligomer comprising in each case a sequence of at least 9 contiguous nucleotides that is complementary to, or hybridizes under moderately stringent or stringent conditions to a treated genomic DNA sequence selected from the group consisting of SEQ ID NOS:40-195, and sequences complementary thereto.
A kit for detecting, or for detecting and distinguishing between or among colorectal cell proliferative disorders, comprising:
A use of a nucleic acid according to any one of claims 11 or 25, of an oligomer or PNA-oligomer according to any one of claims 12 through 14, of a kit according to claim 22, of an array according to any one of claims 19 through 21, of a set of oligonucleotides according to any one of claims 15 through 17, or of a method according to any one of claims 1 through 10, for classifying, distinguishing between or among, diagnosing or determining the predisposition for colorectal cell proliferative disorders.
A use of a nucleic acid according to any one of claims 11 or 25, of an oligomer or PNA-oligomer according to any one of the claims 15 through 17, of a kit according to claim 22, of an array according to any one of the claims 19 through 21, of a set of oligonucleotides according to one of claims 15 through 17, or of a method according to any one of claims 1 through 10, for the therapy of colorectal cell proliferative disorders.
An isolated treated nucleic acid derived from a genomic DNA sequence selected from the group consisting of SEQ ID NOS:1-39, and sequences complementary thereto, wherein the treatment is suitable to convert at least one unmethylated cytosine base of the genomic DNA sequence to uracil or to another base that is detectably dissimilar to cytosine in terms of hybridization.
Dependencies are inferred from the claim text.