Mutational landscape of the transcriptome offers putative targets for immunotherapy of myeloproliferative neoplasms.
Fiorella Schischlik,Roland Jäger,Roland Jäger,Felix Rosebrock,Eva Hug,Michael Schuster,Raimund Holly,Elisabeth Fuchs,Jelena D. Milosevic Feenstra,Edith Bogner,Bettina Gisslinger,Martin Schalling,Elisa Rumi,Daniela Pietra,Gottfried Fischer,Ingrid Fae,Loan Vulliard,Jörg Menche,Torsten Haferlach,Manja Meggendorfer,Anna Stengel,Christoph Bock,Christoph Bock,Mario Cazzola,Heinz Gisslinger,Robert Kralovics,Robert Kralovics +26 more
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TL;DR: This study comprehensively characterize in 113 MPN patients the mutational landscape of the granulocyte transcriptome using RNA-seq data and proposes that mutations derived from splicing defects present in SF3B1 mutated patients may offer an unexplored neoantigen repertoire in MPN.
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About: This article is published in Blood. The article was published on 11 Jul 2019. and is currently open access. The article focuses on the topics: MHC class I.
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Citations
Roles and mechanisms of alternative splicing in cancer - implications for care.
TL;DR: Antisense oligonucleotides offer promise to modulate cancer-relevant alternative splicing decisions, with proof of concept for this type of therapy demonstrated by Nusinersen, a first-in-class treatment for patients with spinal muscular atrophy.
655
Neoantigens: promising targets for cancer therapy
TL;DR: Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames as mentioned in this paper .
Alternative splicing and cancer: a systematic review.
TL;DR: In this paper, a systematic review was conducted to describe the regulatory mechanisms of alternative splicing, as well as its functions in tumor cells, from proliferation and apoptosis to invasion and metastasis, and from angiogenesis to metabolism.
Genetic basis and molecular profiling in myeloproliferative neoplasms.
TL;DR: In this paper , the authors reviewed the recent advances in understanding of the early events after the acquisition of a driver gene mutation and found that the expansion of the clone is the limiting factor that determines the frequency at which MPN disease develops with a long latency.
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Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution
Alba Rodríguez-Meira,Ruggiero Norfo,Simeng Wen,Agathe L. Chédeville,Haseeb Rahman,Jennifer O’Sullivan,Guanlin Wang,Eleni Louka,Warren W. Kretzschmar,Aimee Paterson,Charlotte Brierley,Jean-Edouard Martin,Caroline Demeule,Matthew Bashton,Nikolaos Sousos,Daniela Moralli,Lamia Subha Meem,Joana Carrelha,Wu Bing,Angela Hamblin,Hélène Guermouche,Florence Pasquier,Christophe Marzac,François Girodon,William Vainchenker,Mark W. Drummond,Claire Harrison,J. Ross Chapman,Isabelle Plo,Sten Eirik W. Jacobsen,Bethan Psaila,Supat Thongjuea,Iléana Antony‐Debré,Adam J. Mead +33 more
TL;DR: Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution, highlighting the importance of chronic inflammation in promoting tumor cell fitness and clonal expansion.
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References
Transcriptome Sequencing Reveals Potential Mechanism of Cryptic 3’ Splice Site Selection in SF3B1-mutated Cancers
Christopher DeBoever,Emanuela M. Ghia,Peter J. Shepard,Laura Z. Rassenti,Christian L. Barrett,Kristen Jepsen,Catriona Jamieson,Dennis A. Carson,Thomas J. Kipps,Kelly A. Frazer +9 more
TL;DR: It is proposed that cryptic 3’SS selection is a result of SF3B1 mutations causing a shift in the sterically protected region downstream of the branch point, and this model provides both a mechanistic model consistent with published experimental data and affected targets that will guide further research into the oncogenic effects of SF 3B1 mutation.
Abstract LB-331: Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations
Somasekar Seshagiri,Eric Stawiski,Leonard D. Goldstein,Steffen Durinck,Zora Modrusan,Florian Gnad,Thong T. Nguyen,Bijay S. Jaiswal,Assunta De Rienzo,William G. Richards,Raphael Bueno +10 more
TL;DR: This study significantly expands on the previous genomic studies and provides a comprehensive genomics profile of mesothelioma and identifies several previously unknown alterations and biological pathways that are potential targets for drug discovery and treatment.
Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage
Samar Alsafadi,Alexandre Houy,Aude Battistella,Tatiana Popova,Michel Wassef,Emilie Henry,Franck Tirode,Angelos Constantinou,Sophie Piperno-Neumann,Sergio Roman-Roman,Martin Dutertre,Marc-Henri Stern +11 more
TL;DR: A better understanding of the mechanisms underlying splicing alterations induced by mutant SF3B1 in cancer is provided, and a role for alternative branchpoints in disease is revealed.
The calreticulin ( CALR ) exon 9 mutations are promising targets for cancer immune therapy
Morten Orebro Holmström,Evelina Martinenaite,Shamaila Munir Ahmad,Özcan Met,Christina Friese,Lasse Kjær,Caroline Hasselbalch Riley,P thor Straten,P thor Straten,Inge Marie Svane,Hans Karl Hasselbalch,Mads Hald Andersen,Mads Hald Andersen +12 more
TL;DR: The CALR exon 9 mutations are targets for specific T cells and thus are promising targets for cancer immune therapy such as peptide vaccination in patients harboring CALRExon9 mutations.
Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage
Samar Alsafadi,Alexandre Houy,Aude Battistella,Tatiana Popova,Michel Wassef,Emilie Henry,Franck Tirode,Angelos Constantinou,Sophie Piperno-Neumann,Sergio Roman-Roman,Martin Dutertre,Marc-Henri Stern +11 more
TL;DR: In this paper, the authors used RNA-Seq analyses of uveal melanoma to show that SF3B1(R625/K666) mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3'ss.
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