Methods and Compositions for Diagnosing and Treating Cervical Intraepithelial Neoplasia and Cervical Cancer
AssigneeThe Regents of the University of California
InventorsEri S. Srivatsan, Mysore S. Veena
Life of this patent
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Abstract
Disclosed herein are methods and compositions for diagnosing and treating diseases associated with a loss of cystatin E/M expression including cervical intraepithelial neoplasia and cervical cancer. Genetic mutations and exonic deletions which result in a loss of cystatin E/M expression are also disclosed.
Claims14
A method of diagnosing a subject as having a cancer or identifying a tissue of being cancerous which comprises
- assaying the loss of cystatin E/M expression in a biological sample obtained from the subject or the tissue which comprises
- (a) detecting the presence of a nucleotide mutation in a cystatin E/M gene obtained from the biological sample which corresponds to nucleotide position 91, 155, 185, 374, 437, or 445 of SEQ ID NO:1, or an exonic deletion;
- (b) detecting the presence of an amino acid change in a cystatin E/M protein obtained from the biological sample which corresponds to amino acid position 13, 34, 44, 107, 128, or 131 of SEQ ID NO:2, or a deletion of one or more amino acid residues;
- (c) comparing the amount of the cystatin E/M protein or the amount of mRNA which encodes the cystatin E/M protein obtained from the biological sample with a control or a standard;
- (d) detecting hypermethylation of the promoter of the cystatin E/M gene obtained from the biological sample;
- (e) detecting the presence of a Human Papilloma Viral protein in the biological sample;
- or
- a combination thereof,
- wherein a loss cystatin E/M expression of about 80-100%, preferably about 90-100%, more preferably about 95-100% as compared to a control or standard is indicative of the subject having the cancer or the tissue being cancerous.
An isolated nucleic acid molecule which
- (a) specifically binds to a nucleotide region having at least 15 and up to 40 nucleotide bases, and (al) a nucleotide sequence or its complement having SEQ ID NO:1 with at least one nucleotide mutation selected from the group consisting of A185G, G91A, T437A, A374G, T155C, and C445T, or (a2) a genomic sequence which corresponds to the nucleotide sequence or its complement;
- (b) encodes at least 5 and up to 12 contiguous amino acid residues of an amino acid sequence having SEQ ID NO:2 with at least one amino acid change selected from the group consisting of D44G, A13T, F128Y, H107R, M34T, and L131F;
- (c) specifically binds to a primer sequence that (c1) comprises at least 15 and up to 40 contiguous nucleotide bases of SEQ ID NO:1, a genomic sequence which corresponds to SEQ ID NO:1, or a complement thereof, and (c2) is adjacent to the nucleotide region, or a sequence indicative of encoding SEQ ID NO:1 with at least one amino acid deletion.
An expression profile which provides the expression levels of cystatin E/M in normal tissue, pre-neoplastic tissue, and cancerous tissue.
A method of assaying the loss, if any, of cystatin E/M expression in a biological sample which comprises
- (a) detecting the presence of a nucleotide mutation in a cystatin E/M gene obtained from the biological sample which corresponds to nucleotide position 91, 155, 185, 374, 437, or 445 of SEQ ID NO:1;
- (b) detecting the presence of an amino acid change in a cystatin E/M protein obtained from the biological sample which corresponds to amino acid position 13, 34, 44, 107, 128, or 131 of SEQ ID NO:2;
- (c) comparing the amount of the cystatin E/M protein the amount of mRNA which encodes the cystatin E/M protein obtained from the biological sample with a control or a standard;
- (d) detecting hypermethylation of the promoter of the cystatin E/M gene obtained from the biological sample;
- (e) detecting the presence of a Human Papilloma Viral protein in the biological sample;
- or
- a combination thereof.
Dependencies are inferred from the claim text.