Mutations in the BCR-ABL tyrosine kinase associated with resistance to STI-571
AssigneeThe Regents of the University of California
InventorsCharles L. Sawyers, Mercedes E. Gorre, Neil Pravin Shah, John Nicoll
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Abstract
The invention described herein relates to novel genes and their encoded proteins, termed Mutants Associated with Resistance to STI-571 (e.g., T315I Bcr-Abl), and to diagnostic and therapeutic methods and compositions useful in the management of various cancers that express MARS. The invention further provides methods for identifying molecules that bind to and/or modulate the functional activity of MARS.
Claims20
1-50. (canceled)
A method of detecting the presence of cancer cells that are resistant to treatment with STI-571 in a sample from an individual, comprising:
- (a) determining the identity of a first amino acid at a position of interest in an Abl kinase domain polypeptide in a cancer cell in the sample from the individual;
- and
- (b) comparing the first amino acid with the amino acid sequence shown in SEQ ID NO:
- 1,
- wherein a difference between the first amino acid of the Abl kinase domain polypeptide from the cancer cell and the amino acid shown in SEQ ID NO:
- 1 indicates that the cancer cell is resistant to treatment with STI-571.
A method of detecting a mutant Abl kinase domain polypeptide expressed in a human cancer cell from an individual, comprising:
- (a) determining the sequence of a nucleic acid encoding an Abl kinase domain polypeptide expressed in the human cancer cell;
- and
- (b) comparing the amino acid sequence encoded by the nucleic acid with the amino acid sequence shown as SEQ ID NO:
- 1 to detect the presence of a mutation,
- wherein the mutation is associated with resistance of the cancer cell to STI-571.
Dependencies are inferred from the claim text.