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The Role of RNAs in Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 2443

Special Issue Editor


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Guest Editor
Ares Pharmaceuticals, Saint Paul, MN, USA
Interests: cancer cell; cell biology; cell signaling; gene expression; PCR

Special Issue Information

Dear Colleagues,

Significant advances in RNA-based next-generation sequencing, single-cell transcriptomics, and third-generation long-read sequencing technologies have provided unprecedented depth and scope for understanding the role of RNA processing in diagnostics and leveraging potential new modes of therapies for undruggable targets in cancers. RNA-seq methods have led to the discovery of novel biomarkers in identifying differentially expressed miRNA, lncRNA, circRNA and fusion transcripts, enabling highly granular molecular characterizations of cancer subtypes that promise to actualize personalized medicine. Advances in separation science and nanotechnology platforms have helped to overcome some drawbacks of introducing RNA molecules into the body, such as the rapid degradation in human tissues; eliciting immunogenicity and Impermeability across membranes, promoting clinical trials for RNA-based therapeutics. A range of therapeutic options are being developed including: antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA, aptamers, mRNA replacement and mRNA vaccines. This Special Issue reports on recent advances in RNA biology that will expand diagnostic and therapeutic capabilities for treating cancers.

Dr. Sanjive Qazi
Guest Editor

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Keywords

  • RNA biology
  • next generation sequencing
  • RNA based therapeutics personalized medicine
  • nanotechnology
  • cancers

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Published Papers (1 paper)

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Research

21 pages, 4494 KiB  
Article
A New Approach of Detecting ALK Fusion Oncogenes by RNA Sequencing Exon Coverage Analysis
by Galina Zakharova, Maria Suntsova, Elizaveta Rabushko, Tharaa Mohammad, Alexey Drobyshev, Alexander Seryakov, Elena Poddubskaya, Alexey Moisseev, Anastasia Smirnova, Maxim Sorokin, Victor Tkachev, Alexander Simonov, Egor Guguchkin, Evgeny Karpulevich and Anton Buzdin
Cancers 2024, 16(22), 3851; https://doi.org/10.3390/cancers16223851 - 16 Nov 2024
Viewed by 2031
Abstract
Background: In clinical practice, various methods are used to identify ALK gene rearrangements in tumor samples, ranging from “classic” techniques, such as IHC, FISH, and RT-qPCR, to more advanced highly multiplexed approaches, such as NanoString technology and NGS panels. Each of these methods [...] Read more.
Background: In clinical practice, various methods are used to identify ALK gene rearrangements in tumor samples, ranging from “classic” techniques, such as IHC, FISH, and RT-qPCR, to more advanced highly multiplexed approaches, such as NanoString technology and NGS panels. Each of these methods has its own advantages and disadvantages, but they share the drawback of detecting only a restricted (although sometimes quite extensive) set of preselected biomarkers. At the same time, whole transcriptome sequencing (WTS, RNAseq) can, in principle, be used to detect gene fusions while simultaneously analyzing an incomparably wide range of tumor characteristics. However, WTS is not widely used in practice due to purely analytical limitations and the high complexity of bioinformatic analysis, which requires considerable expertise. In particular, methods to detect gene fusions in RNAseq data rely on the identification of chimeric reads. However, the typically low number of true fusion reads in RNAseq limits its sensitivity. In a previous study, we observed asymmetry in the RNAseq exon coverage of the 3′ partners of some fusion transcripts. In this study, we conducted a comprehensive evaluation of the accuracy of ALK fusion detection through an analysis of differences in the coverage of its tyrosine kinase exons. Methods: A total of 906 human cancer biosamples were subjected to analysis using experimental RNAseq data, with the objective of determining the extent of asymmetry in ALK coverage. A total of 50 samples were analyzed, comprising 13 samples with predicted ALK fusions and 37 samples without predicted ALK fusions. These samples were assessed by targeted sequencing with two NGS panels that were specifically designed to detect fusion transcripts (the TruSight RNA Fusion Panel and the OncoFu Elite panel). Results: ALK fusions were confirmed in 11 out of the 13 predicted cases, with an overall accuracy of 96% (sensitivity 100%, specificity 94.9%). Two discordant cases exhibited low ALK coverage depth, which could be addressed algorithmically to enhance the accuracy of the results. It was also important to consider read strand specificity due to the presence of antisense transcripts involving parts of ALK. In a limited patient sample undergoing ALK-targeted therapy, the algorithm successfully predicted treatment efficacy. Conclusions: RNAseq exon coverage analysis can effectively detect ALK rearrangements. Full article
(This article belongs to the Special Issue The Role of RNAs in Cancers)
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