guest ::
| Home > Publications database > Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. |
| Home > Publications database > Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. |
| Journal Article | DKFZ-2017-03664 |
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
2014
Cell Press
Cambridge, Mass.
This record in other databases: 
Please use a persistent id in citations: doi:10.1016/j.ccr.2014.02.004
Abstract: Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.
Keyword(s): Biphenyl Compounds ; GLI2 protein, human ; Hedgehog Proteins ; Kruppel-Like Transcription Factors ; LDE225 ; MYCN protein, human ; N-Myc Proto-Oncogene Protein ; Nuclear Proteins ; Oncogene Proteins ; PTCH protein, human ; Patched Receptors ; Patched-1 Receptor ; Ptch1 protein, mouse ; Pyridines ; Receptors, Cell Surface ; Receptors, G-Protein-Coupled ; Repressor Proteins ; SHH protein, human ; SMO protein, human ; SUFU protein, human ; Smoothened Receptor ; TP53 protein, human ; Tumor Suppressor Protein p53 ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; TERT protein, human ; Telomerase ; DDX3X protein, human ; DEAD-box RNA Helicases
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
|
The record appears in these collections: |
