Evasion of cell senescence in SHH medulloblastoma
| العنوان: | Evasion of cell senescence in SHH medulloblastoma |
|---|---|
| المؤلفون: | Frédéric Charron, Shannon M. Swikert, Lukas Tamayo-Orrego |
| المصدر: | Cell Cycle |
| بيانات النشر: | Informa UK Limited, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Senescence, Genome instability, preneoplasia, medicine.disease_cause, Loss of heterozygosity, sonic hedgehog, 03 medical and health sciences, Ptch1, medicine, Animals, Humans, Hedgehog Proteins, TP53, Sonic hedgehog, neoplasms, Molecular Biology, Cellular Senescence, Genetics, Medulloblastoma, Extra Views, biology, p53, Cell Biology, medicine.disease, Hedgehog signaling pathway, nervous system diseases, stomatognathic diseases, 030104 developmental biology, PTCH1, cell senescence, Mutation, Cancer research, biology.protein, Tumor Suppressor Protein p53, Carcinogenesis, Signal Transduction, Developmental Biology |
| الوصف: | The mechanisms leading to brain tumor formation are poorly understood. Using Ptch1+/− mice as a medulloblastoma model, sequential mutations were found to shape tumor evolution. Initially, medulloblastoma preneoplastic lesions display loss of heterozygosity of the Ptch1 wild-type allele, an event associated with cell senescence in preneoplasia. Subsequently, p53 mutations lead to senescence evasion and progression from preneoplasia to medulloblastoma. These findings are consistent with a model where high levels of Hedgehog signaling caused by the loss of the tumor suppressor Ptch1 lead to oncogene-induced senescence and drive p53 mutations. Thus, cell senescence is an important characteristic of a subset of SHH medulloblastoma and might explain the acquisition of somatic TP53 mutations in human medulloblastoma. This mode of medulloblastoma formation contrasts with the one characterizing Li-Fraumeni patients with medulloblastoma, where TP53 germ-line mutations cause chromothriptic genomic instability and lead to mutations in Hedgehog signaling genes, which drive medulloblastoma growth. Here we discuss in detail these 2 alternative mechanisms leading to medulloblastoma tumorigenesis. |
| تدمد: | 1551-4005 1538-4101 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5dc10099687a4223936d0c2abd20d41Test https://doi.org/10.1080/15384101.2016.1189044Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b5dc10099687a4223936d0c2abd20d41 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15514005 15384101 |
|---|