Altered RNA processing in cancer pathogenesis and therapy Review
| Authors: | Obeng, E. A.; Stewart, C.; Abdel-Wahab, O. |
| Review Title: | Altered RNA processing in cancer pathogenesis and therapy |
| Abstract: | Major advances in our understanding of cancer pathogenesis and therapy have come from efforts to catalog genomic alterations in cancer. A growing number of large-scale genomic studies have uncovered mutations that drive cancer by perturbing cotranscrip-tional and post-transcriptional regulation of gene expression. These include alterations that affect each phase of RNA processing, including splicing, transport, editing, and decay of messenger RNA. The discovery of these events illuminates a number of novel therapeutic vulnerabilities generated by aberrant RNA processing in cancer, several of which have progressed to clinical development. Significance: There is increased recognition that genetic alterations affecting RNA splicing and polyadenylation are common in cancer and may generate novel therapeutic opportunities. Such mutations may occur within an individual gene or in RNA processing factors themselves, thereby influencing splicing of many downstream target genes. This review discusses the biological impact of these mutations on tumorigenesis and the therapeutic approaches targeting cells bearing these mutations. ©2019 American Association for Cancer Research. |
| Keywords: | vasculotropin; protein expression; gene mutation; single nucleotide polymorphism; gene deletion; review; nonhuman; protein localization; gene expression; genotype; in vitro study; cancer therapy; rna binding protein; gene expression regulation; oncogene; myelodysplastic syndrome; immunoglobulin heavy chain; messenger rna; genomic instability; dna damage response; hematopoiesis; 3' untranslated region; catalysis; spliceosome; cyclin d1; rna processing; chronic lymphatic leukemia; zinc finger protein; loss of function mutation; cd19 antigen; transesterification; rna splicing; chromosome 17q; pyrimidine; protein mdm2; rna sequence; programmed death 1 ligand 1; programmed death 1 receptor; molecular pathology; polyadenylation; acute myeloid leukemia; small nuclear rna; antisense therapy; cell cycle protein 6; refractory anemia with ringed sideroblasts; protein bcl x; tumor immunogenicity; ibrutinib; monoclonal b cell lymphocytosis; human; sf3b1 gene; venetoclax; whole exome sequencing; clinical development plan; rna recognition motif; intron retention; splicing factor u2af; u2af1 gene; zrsr2 gene; polypyrimidine tract binding protein; rg 3039; refractory cytopenia with multilineage dysplasia and ringed sideroblasts |
| Journal Title: | Cancer Discovery |
| Volume: | 9 |
| Issue: | 11 |
| ISSN: | 2159-8274 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2019-11-01 |
| Start Page: | 1493 |
| End Page: | 1510 |
| Language: | English |
| DOI: | 10.1158/2159-8290.Cd-19-0399 |
| PUBMED: | 31611195 |
| PROVIDER: | scopus |
| PMCID: | PMC6825565 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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