Genome-wide colocalization of RNA-DNA interactions and fusion RNA pairs

Proceedings of the National Academy of Sciences of the United States of America
Zhangming YanSheng Zhong

Abstract

Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA-DNA interactions mapped in two normal, noncancerous cell types [using iMARGI, an enhanced version of the mapping of RNA-genome interactions (MARGI) assay]. Among the top 10 most significant RNA-DNA interactions in normal cells, 5 colocalized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA-DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA-DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA sequencing (RNA-seq). Thirty-seven of 42 fusion transcripts in the validation cohort were found to exhibit RNA-DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a ca...Continue Reading

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Citations

Oct 18, 2019·Nature Protocols·Weixin WuSheng Zhong
Aug 9, 2020·Nature Reviews. Genetics·Dali ZongAndré Nussenzweig
Mar 30, 2020·Science China. Life Sciences·Cong LiuZhihua Zhang
May 31, 2020·Non-coding RNA·Masaki Kato, Piero Carninci
Sep 26, 2020·Nucleic Acids Research·Volodymyr TsybulskyiIrmtraud M Meyer
Oct 17, 2020·Nature Communications·Riccardo CalandrelliSheng Zhong
Dec 14, 2019·Genes & Diseases·Hao WuHui Li

Methods Mentioned

BETA
RNA-seq
PCR
FuseFISH
pulldown
membrane filtration
fluorescence imaging

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