The evolution of alternative splicing in glioblastoma under therapy
| العنوان: | The evolution of alternative splicing in glioblastoma under therapy |
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| المؤلفون: | Lin Wang, Francisca Catalan, Hideho Okada, Karin Shamardani, Aaron Diaz, Susan M. Chang, Joanna J. Phillips, Takahide Nejo, Husam Babikir |
| المصدر: | Genome Biology Genome Biology, Vol 22, Iss 1, Pp 1-15 (2021) Genome biology, vol 22, iss 1 |
| بيانات النشر: | BioMed Central, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_treatment, T-Lymphocytes, Stem Cell Research - Nonembryonic - Human, Gene expression, Protein Isoforms, lcsh:QH301-705.5, Cancer, Brain Neoplasms, Intracellular Signaling Peptides and Proteins, Brain, RNA-Binding Proteins, Biological Sciences, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, RNA splicing, Biotechnology, lcsh:QH426-470, Evolution, Bioinformatics, T cell, Biology, Protein Serine-Threonine Kinases, Evolution, Molecular, Rare Diseases, Clinical Research, Information and Computing Sciences, Genetics, medicine, Humans, Gene, Neoplastic, Research, Alternative splicing, Neurosciences, Molecular, RNA, Immunotherapy, Stem Cell Research, Human genetics, Brain Disorders, Brain Cancer, lcsh:Genetics, Alternative Splicing, Orphan Drug, Gene Expression Regulation, lcsh:Biology (General), Cancer research, Immunization, Glioblastoma, Environmental Sciences |
| الوصف: | Background Alternative splicing is a rich source of tumor-specific neoantigen targets for immunotherapy. This holds promise for glioblastomas (GBMs), the most common primary tumors of the adult brain, which are resistant to standard-of-care therapy. Although most clinical trials enroll patients at recurrence, most preclinical studies have been done with specimens from primary disease. There are limited expression data from GBMs at recurrence and surprisingly little is known about the evolution of splicing patterns under therapy. Result We profile 37 primary-recurrent paired human GBM specimens via RNA sequencing. We describe the landscape of alternative splicing in GBM at recurrence and contrast that to primary and non-malignant brain-tissue specimens. By screening single-cell atlases, we identify cell-type-specific splicing patterns and novel splicing events in cell-surface proteins that are suitable targets for engineered T cell therapies. We identify recurrent-specific isoforms of mitogen-activated kinase pathway genes that enhance invasiveness and are preferentially expressed by stem-like cells. Conclusion These studies shed light on gene expression in recurrent GBM and identify novel targets for therapeutic development. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1474-760X 1474-7596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8708512671fe5df0718c196c80330ac0Test http://europepmc.org/articles/PMC7835670Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8708512671fe5df0718c196c80330ac0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1474760X 14747596 |
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