Adapter gene
AssigneeThe Hospital for Sick Children
InventorsJane McGlade, Michael Loreto
Life of this patent
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Abstract
The present invention relates to the identification and cloning of a novel gene, MARS (Modulator of Antigen Receptor Signaling), which is a putative tumor suppressor gene. The present invention also relates to the relation of the MARS gene to human cancers and its use in the diagnosis and prognosis of human cancer. The invention also relates to the therapy of human cancers which have a mutation in the MARS gene, or lack the MARS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.
Claims47
An isolated MARS gene sequence consisting of 7 exons and 6 introns, of which exons 2 and 3 code for a SH3 domain and exons 4 and 5 code for a SH2 domain, said gene being localized to chromosome 20q11.
An isolated nucleic acid selected from the group consisting of;
- a) a nucleic acid sequence encoding a biologically active mammalian MARS protein;
- b) a nucleic acid sequence encoding a MARS gene sequence;
- c) a nucleic acid sequence encoding a MARS cDNA sequence;
- d) a nucleic acid sequence-sharing at least 85% sequence identity with a), b) or c);
- e) a nucleic acid sequence which hybridizes under moderate to high stringency with a), b) c) or d);
- f) a nucleic acid complementary to any one of a) to e);
- g) a nucleic acid degeneracy equivalent to any one of a) to f);
- and
- h) a nucleic acid fragment of any one of a) to g) exhibiting MARS biological activity.
An isolated MARS protein or fragment thereof.
A method for the treatment of a malignant disorder in a subject characterized by a decrease or lack of MARS protein function, said method comprising the steps of;
- administering to said subject a MARS protein or peptide exhibiting biological MARS activity.
A method for screening a subject for an alteration of a MARS gene which method comprises;
- comparing the sequence of a MARS gene or MARS RNA in a germline or somatic tissue or cell sample from said subject or a sequence of MARS cDNA made from mRNA in said sample with a normal MARS gene sequence encoding an amino acid sequence of SEQ ID NO:5,
- wherein a difference in the sequence of the MARS gene, MARS RNA or MARS cDNA of the subject from the normal indicates an alteration in the MARS gene in said subject.
A method for identifying compounds which can modulate the expression of a MARS gene comprising
- contacting a cell with a candidate compound wherein said cell includes a regulatory region of a MARS gene operably joined to a coding region;
- and
- detecting a change in expression of said coding region.
A method for identifying compounds which can selectively bind to a MARS protein comprising the steps of
- providing a preparation including at least one MARS protein or or portion thereof;
- contacting said preparation with a sample including at least one candidate compound;
- and
- detecting binding of said MARS protein or portion thereof to said candidate compound.
A method for identifying compounds which can modulate activity of a MARS protein comprising the steps of
- contacting a cell expressing a normal or mutant MARS protein with at least one candidate compound;
- and
- detecting a change in a marker of said activity.
A kit for screening for an alteration in MARS gene in a human subject which comprises at least one antibody which specifically binds to a wild-type MARS polypeptide but not a variant MARS polypeptide or which specifically binds to an epitope of a variant MARS polypeptide.
A kit for screening for an alteration in MARS gene in a human subject which comprises at least one oligonucleotide which specifically binds to a wild-type MARS nucleic acid sequence but not a variant MARS nucleic acid sequence or which specifically binds to a variant MARS nucleic acid sequence.
Use of a MARS protein or of a peptide exhibiting biological MARS activity for the preparation of a medicament for the treatment of a malignant disorder.
Use of a nucleotide sequence encoding a MARS protein or a peptide exhibiting biological MARS activity for the preparation of a medicament for the treatment of a malignant disorder.
Dependencies are inferred from the claim text.