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Series GSE217126 Query DataSets for GSE217126
Status Public on May 02, 2023
Title Circular RNAs drive oncogenic chromosomal translocations through R-loop-mediated genome instability [ncRNA-seq]
Organism Homo sapiens
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Studying the role of circular RNAs in cancer initiation by profiling the interaction of circRNAs with DNA in human cells. The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in leukaemia is the formation of a potent oncogene by chromosomal translocations between the histone methyltransferase Mixed Lineage Leukaemia (MLL) gene and one of over 100 translocation partner genes. Here we show that circular RNAs (circRNAs) - which are a family of covalently-closed, alternatively-spliced RNA molecules - bind DNA, forming circRNA:DNA hybrids (circR-loops) at their cognate loci, and promote transcriptional pausing and DNA breaks. The MLL recombinome concentrates these circR-loops and by overexpressing circRNAs from MLL in human cells we could generate de novo chromosomal translocations, mimicking the MLL recombinome. We anticipate our findings will illuminate this critical phase in cancer initiation and provide a framework to investigate the action of endogenous RNA molecules underlying various genetic aberrations through a process of Endogenous RNA-Directed DNA Damage (ER3D).
Overall design Guthrie cards/neonatal blood spots from 8 control individuals (with no known blood, or other cancer) and 8 individuals who developed infant leukemia under the age of 10 associated with rearrangements in the MLL gene.
Contributor(s) Marri S, Conn SJ
Citation(s) 37295428
Submission date Nov 02, 2022
Last update date Aug 01, 2023
Contact name Simon Conn
Organization name Flinders University
Department College of Medicine and Public Health
Lab Circular RNAs in Cancer Laboratory
Street address Sturt Road, Bedford Park
City Adelaide
State/province South Australia
ZIP/Postal code 5042
Country Australia
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (16)
GSM6705464 1729808
GSM6705465 1729804
GSM6705466 1729802
This SubSeries is part of SuperSeries:
GSE125986 Circular RNAs drive oncogenic chromosomal translocations through R-loop-mediated genome instability
BioProject PRJNA896982

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Supplementary file Size Download File type/resource
GSE217126_Junction_Read_counts.txt.gz 431.9 Kb (ftp)(http) TXT
GSE217126_Raw_counts.txt.gz 498.7 Kb (ftp)(http) TXT
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