The ever-changing world of gene fusions in cancer: a secondary gene fusion and progression

Powers, Maureen A.

doi:10.1038/s41388-019-1057-2

Cited by 22 publications

(17 citation statements)

References 12 publications

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“…Because gene fusions have diagnostic, therapeutic, and prognostic significance, 37,38 substantial efforts have been made to validate high‐throughput platforms that can recognize multiple oncogenic gene fusions in clinical specimens. Patients with advanced cancers are not candidates for curative surgical excision; hence, minimally invasive procedures such as core‐needle biopsy (CNB) and/or FNA are the typical means of tumor sampling for diagnosis and molecular studies 34,39 .…”

Section: Discussionmentioning

confidence: 99%

Utilization of cytology smears improves success rates of RNA‐based next‐generation sequencing gene fusion assays for clinically relevant predictive biomarkers

Ramani

Chen

Broaddus

et al. 2020

Cancer Cytopathology

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Background The use of RNA‐based next‐generation sequencing (NGS) assays to detect gene fusions for targeted therapy has rapidly become an essential component of comprehensive molecular profiling. For cytology specimens, the cell block (CB) is most commonly used for fusion testing; however, insufficient cellularity and/or suboptimal RNA quality are often limiting factors. In the current study, the authors evaluated the factors affecting RNA fusion testing in cytology and the added value of smears in cases with a suboptimal or inadequate CB. Methods A 12‐month retrospective review was performed to identify cytology cases that were evaluated by a targeted RNA‐based NGS assay. Samples were sequenced by targeted amplicon‐based NGS for 51 clinically relevant genes on a proprietary platform. Preanalytic factors and NGS quality parameters were correlated with the results of RNA fusion testing. Results The overall success rate of RNA fusion testing was 92%. Of the 146 cases successfully sequenced, 14% had a clinically relevant fusion detected. NGS testing success positively correlated with RNA yield (P = .03) but was independent of the tumor fraction, the tumor size, or the number of slides used for extraction. CB preparations were adequate for testing in 45% cases, but the inclusion of direct smears increased the adequacy rate to 92%. There was no significant difference in testing success rates between smears and CB preparations. Conclusions The success of RNA‐based NGS fusion testing depends on the quality and quantity of RNA extracted. The use of direct smears significantly improves the adequacy of cytologic samples for RNA fusion testing for predictive biomarkers.

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Section: Discussionmentioning

confidence: 99%

Utilization of cytology smears improves success rates of RNA‐based next‐generation sequencing gene fusion assays for clinically relevant predictive biomarkers

Ramani

Chen

Broaddus

et al. 2020

Cancer Cytopathology

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“…The role of chromosomal translocations leading to the production of fusion gene products is well-known phenomenon in cancer, with examples including BCR-ABL and PML-RARA [33] with the resulting fusion protein contributing to or even driving oncogenesis. Recently evidence has emerged of chromosomal translocations leading to the formation of novel fusion circRNAs, which can drive oncogenesis.…”

Section: Fusion Circrnas In Cancermentioning

confidence: 99%

Insights into the Evolving Roles of Circular RNAs in Cancer

Harper

Mottram

Whitehouse

2021

Cancers

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The majority of RNAs transcribed from the human genome have no coding capacity and are termed non-coding RNAs (ncRNAs). It is now widely accepted that ncRNAs play key roles in cell regulation and disease. Circular RNAs (circRNAs) are a form of ncRNA, characterised by a closed loop structure with roles as competing endogenous RNAs (ceRNAs), protein interactors and transcriptional regulators. Functioning as key cellular regulators, dysregulated circRNAs have a significant impact on disease progression, particularly in cancer. Evidence is emerging of specific circRNAs having oncogenic or tumour suppressive properties. The multifaceted nature of circRNA function may additionally have merit as a novel therapeutic target, either in treatment or as a novel biomarker, due to their cell-and disease-state specific expression and long-term stability. This review aims to summarise current findings on how circRNAs are dysregulated in cancer, the effects this has on disease progression, and how circRNAs may be targeted or utilised as future potential therapeutic options.

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“…This type of classification underpins the function through which different variants associate with disease etiology. For example, functional variants that occur in transcribed portions of the genome generally associate with altered transcript message or function (manifested as modified exonic sequences, alternative splicing, modified UTRs, altered ncRNA folding and/or gene fusions [96][97][98]). Interestingly, most GWAS/transcribed regulatory variants are not limited to protein coding genes but primarily localize in transcribed non-coding sequences that may generate regulatory transcripts with low or no protein coding potential [99][100][101][102].…”

Section: Functional Classification Of Mutations In Cancermentioning

confidence: 99%

Non-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine

Lange

Begolli

Giakountis

2021

ncRNA

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The cancer genome is characterized by extensive variability, in the form of Single Nucleotide Polymorphisms (SNPs) or structural variations such as Copy Number Alterations (CNAs) across wider genomic areas. At the molecular level, most SNPs and/or CNAs reside in non-coding sequences, ultimately affecting the regulation of oncogenes and/or tumor-suppressors in a cancer-specific manner. Notably, inherited non-coding variants can predispose for cancer decades prior to disease onset. Furthermore, accumulation of additional non-coding driver mutations during progression of the disease, gives rise to genomic instability, acting as the driving force of neoplastic development and malignant evolution. Therefore, detection and characterization of such mutations can improve risk assessment for healthy carriers and expand the diagnostic and therapeutic toolbox for the patient. This review focuses on functional variants that reside in transcribed or not transcribed non-coding regions of the cancer genome and presents a collection of appropriate state-of-the-art methodologies to study them.

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The ever-changing world of gene fusions in cancer: a secondary gene fusion and progression

Cited by 22 publications

References 12 publications

Utilization of cytology smears improves success rates of RNA‐based next‐generation sequencing gene fusion assays for clinically relevant predictive biomarkers

Utilization of cytology smears improves success rates of RNA‐based next‐generation sequencing gene fusion assays for clinically relevant predictive biomarkers

Insights into the Evolving Roles of Circular RNAs in Cancer

Non-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine

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