Amplification of human MDM2 gene in human tumors
AssigneeThe Johns Hopkins University
InventorsKenneth W. Kinzler, Bert Vogelstein
Life of this patent
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Abstract
A human gene has been discovered which is genetically altered in human tumor cells. The genetic alteration is gene amplification and leads to a corresponding increase in gene products. Detecting that the gene, designated hMDM2, has become amplified or detecting increased expression of gene products is diagnostic of tumorigenesis. Human MDM2 protein binds to human p53 and allows the cell to escape from p53-regulated
Claims55
A method of diagnosing a neoplastic tissue in a human comprising:
- detecting amplification of human MDM2 gene or elevated expression of a human MDM2 gene product in a tissue or body fluid isolated from a human, wherein amplification of the human MDM2 gene or elevated expression of human MDM2 gene product provides a diagnosis of neoplasia or the potential for neoplastic development.
A cDNA molecule comprising nucleotides 1 to 2372, as shown in FIG. 1, or fragments thereof, consisting of at least 14 contiguous nucleotides.
Human MDM2 protein substantially free of other human proteins.
A preparation of antibodies specifically immunoreactive with human MDM2 protein.
A nucleotide probe comprising a sequence of at least 10 nucleotides which are complementary to nucleotides 1-2372 of human MDM2 gene, as shown in FIG. 1.
A kit for detecting the amplification of a human MDM2 gene in a human tissue or body fluid sample comprising:
- a nucleic acid probe capable of hybridizing to said human MDM2 gene under conditions of high stringency, and instructions for determining said amplification.
A kit for detecting elevated expression of a human MDM2 mRNA in a human tissue or body fluid sample comprising:
- a nucleic acid probe capable of hybridizing to said mRNA, and written instructions for determining elevated expression of mRNA.
A kit for detecting elevated expression of a human MDM2 protein in a human tissue or body fluid sample comprising MDM2 protein-specific antibodies and written instructions for determining elevated expression of human MDM2 protein.
A method of treating a neoplastic cell or a cell having neoplastic potential, comprising:
- administering to a cell a therapeutically effective amount of an inhibitory compound which interferes with the expression of human MDM2 gene.
A method for identifying compounds which interfere with the binding of human MDM-2 to human p53, comprising:
- binding a predetermined quantity of a first human protein which is detectably labelled to a second human protein;
- adding a compound to be tested for its capacity to inhibit binding of said first and second proteins to each other;
- determining the quantity of the first human protein which is displaced from or prevented from binding to the second human protein;
- wherein the first human protein is MDM-2 and the second human protein is p53 or the first human protein is p53 and the second human protein is MDM-2.
A method for inhibiting the growth of tumor cells which contain a human MDM2 gene amplification, comprising:
- administering a polypeptide to tumor cells which contain a human MDM2 gene amplification, said polyptide consisting essentially of a portion of p53, said portion comprising amino acids 13-41 of p53, said polypeptide being capable of binding to human MDM2.
A method for inhibiting the growth of tumor cells which contain a human MDM2 gene amplification, comprising:
- administering to tumor cells which contain a human MDM2 gene amplification a DNA molecule which expresses a polypeptide consisting essentially of a portion of p53, said portion comprising amino acids 13-41 of p53, said polypeptide being capable of binding to human MDM2.
A polypeptide consisting essentially of a portion of p53, said portion comprising amino acids 13-41 of p53, said polypeptide capable of binding to human MDM2.
A hybridoma cell having the identifying characteristics of ED9 (ATCC HB 11291).
A hybridoma cell having the identifying characteristics of IF2 (ATCC HB 11290).
Dependencies are inferred from the claim text.