دورية أكاديمية
Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma
| العنوان: | Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma |
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| المؤلفون: | Suzuki H., Kumar S. A., Shuai S., Diaz-Navarro A., Gutierrez-Fernandez A., De Antonellis P., Cavalli F. M. G., Juraschka K., Farooq H., Shibahara I., Vladoiu M. C., Zhang J., Abeysundara N., Przelicki D., Skowron P., Gauer N., Luu B., Daniels C., Wu X., Forget A., Momin A., Wang J., Dong W., Kim S. -K., Grajkowska W. A., Jouvet A., Fevre-Montange M., Garre M. L., Nageswara Rao A. A., Giannini C., Kros J. M., French P. J., Jabado N., Ng H. -K., Poon W. S., Eberhart C. G., Pollack I. F., Olson J. M., Weiss W. A., Kumabe T., Lopez-Aguilar E., Lach B., Massimino M., Van Meir E. G., Rubin J. B., Vibhakar R., Chambless L. B., Kijima N., Klekner A., Bognar L., Chan J. A., Faria C. C., Ragoussis J., Pfister S. M., Goldenberg A., Wechsler-Reya R. J., Bailey S. D., Garzia L., Morrissy A. S., Marra M. A., Huang X., Malkin D., Ayrault O., Ramaswamy V., Puente X. S., Calarco J. A., Stein L., Taylor M. D. |
| المساهمون: | Suzuki, H., Kumar, S. A., Shuai, S., Diaz-Navarro, A., Gutierrez-Fernandez, A., De Antonellis, P., Cavalli, F. M. G., Juraschka, K., Farooq, H., Shibahara, I., Vladoiu, M. C., Zhang, J., Abeysundara, N., Przelicki, D., Skowron, P., Gauer, N., Luu, B., Daniels, C., Wu, X., Forget, A., Momin, A., Wang, J., Dong, W., Kim, S. -K., Grajkowska, W. A., Jouvet, A., Fevre-Montange, M., Garre, M. L., Nageswara Rao, A. A., Giannini, C., Kros, J. M., French, P. J., Jabado, N., Ng, H. -K., Poon, W. S., Eberhart, C. G., Pollack, I. F., Olson, J. M., Weiss, W. A., Kumabe, T., Lopez-Aguilar, E., Lach, B., Massimino, M., Van Meir, E. G., Rubin, J. B., Vibhakar, R., Chambless, L. B., Kijima, N., Klekner, A., Bognar, L., Chan, J. A., Faria, C. C., Ragoussis, J., Pfister, S. M., Goldenberg, A., Wechsler-Reya, R. J., Bailey, S. D., Garzia, L., Morrissy, A. S., Marra, M. A., Huang, X., Malkin, D., Ayrault, O., Ramaswamy, V., Puente, X. S., Calarco, J. A., Stein, L., Taylor, M. D. |
| سنة النشر: | 2019 |
| المجموعة: | IRIS Università degli Studi di Napoli Federico II |
| مصطلحات موضوعية: | Adolescent, Adult, Alternative Splicing, Cerebellar Neoplasm, Hedgehog Protein, Human, Medulloblastoma, Mutation, RNA Splice Site, RNA Splicing, RNA, Small Nuclear |
| الوصف: | In cancer, recurrent somatic single-nucleotide variants—which are rare in most paediatric cancers—are confined largely to protein-coding genes1–3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5′ splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5′ cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | volume:574; issue:7780; firstpage:707; lastpage:711; numberofpages:5; journal:NATURE; https://hdl.handle.net/11588/900830Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85074231650 |
| DOI: | 10.1038/s41586-019-1650-0 |
| الإتاحة: | https://doi.org/10.1038/s41586-019-1650-0Test https://hdl.handle.net/11588/900830Test |
| رقم الانضمام: | edsbas.AB93D23 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41586-019-1650-0 |
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