HUMAN NOTCH RECEPTOR MUTATIONS AND THEIR APPLICATION

摘要

1. A method for identifying solid tumor cells in which there is an increased level of signal transmission via the NOTCH receptor, comprising determining whether said cells contain a mutation in a domain rich in proline, glutamate, serine, threonine (PEST), human NOTCH receptor, or in the TAD domain human NOTCH1 receptor, wherein said solid tumor cells are selected from the group consisting of: lung tumor, glioma, gastrointestinal tumor, kidney tumor, ovarian tumor, liver tumor, colon and rectum tumor, op endometrial holi, kidney tumors, prostate tumors, thyroid tumors, neuroblastomas, pancreatic tumors, glioblastoma multiformes, cervical tumors, stomach tumors, bladder tumors, hepatomas, breast tumors, colon tumors, melanomas, bile duct tumors and tumors of the head and neck. 2. A method for determining whether a patient diagnosed with cancer should administer a NOTCH inhibitor, including determining whether tumor cells from said patient contain an activating mutation in the PEST domain or in the TAD domain of the human NOTCH receptor, the presence of the indicated mutation indicating that the response of the indicated patient to treatment with a NOTCH inhibitor will be favorable. 3. A method according to claim 1 or 2, characterized in that said NOTCH receptor is NOTCH1 or NOTCH3.4. A method according to claim 1 or 2, characterized in that said mutation is a) a missense mutation, a nonsense mutation or a mutation with a reading frame shift; b) a mutation with a reading frame shift or a nonsense mutation in the PEST domain; c) a deletion in nucleotide 7279 in the human NOTCH1 gene; d)