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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Pan-Tissue and -Cancer Analysis of ROR1 and ROR2 Transcript Variants Identify Novel Functional Significance for an
1Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Women's and Children's Health, Faculty of Medicine and Health, University of New South Wales, Cnr High and Botany St., Kensington, Sydney, NSW 2052, Australia.
Abstract:
ROR1/2 are putative druggable targets increasing in significance in translational oncology. Expression of ROR1/2 mRNA and transcript variants has not been systematically examined thus far. ROR1/2 transcript variant sequences, signal peptides for cell surface localisation, and mRNA and transcript variant expression were examined in 34 transcriptomic datasets including 33 cancer types and 54 non-diseased human tissues. ROR1/2 have four and eight transcript variants, respectively. ROR1/2 mRNA and transcript variant expression was detected in various non-diseased tissues. Our analysis identifies predominant expression of ROR1 transcript variant ENST00000545203, which lacks a signal peptide for cell surface localisation, rather than the predicted principal variant ENST00000371079. ENST00000375708 is the predominantly expressed transcript variant of ROR2. ROR1/2 expression in healthy human tissues should be carefully considered for safety assessment of targeted therapy. Studies exploring the function and significance of the predominantly expressed ROR1 transcript variant ENST00000545203 are warranted.
Insights
ROR1 and ROR2 are key targets in cancer therapy. This study reveals their varied expression patterns and identifies a predominant ROR1 variant lacking cell surface localization, impacting targeted therapy safety.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Receptor tyrosine kinase-like orphan receptor 1 (ROR1) and ROR2 are increasingly recognized as significant druggable targets in translational oncology.
- Systematic examination of ROR1/2 mRNA and transcript variant expression has been lacking.
Purpose of the Study:
- To systematically analyze ROR1/2 mRNA and transcript variant expression across diverse human tissues and cancer types.
- To identify predominant transcript variants and assess their potential for cell surface localization.
Main Methods:
- Analysis of ROR1/2 transcript variant sequences and predicted signal peptides.
- Examination of mRNA and transcript variant expression in 34 transcriptomic datasets (33 cancer types, 54 non-diseased tissues).
Main Results:
- ROR1 has four and ROR2 has eight transcript variants, with expression detected in various non-diseased tissues.
- Predominant ROR1 expression is from variant ENST00000545203 (lacks signal peptide), not the predicted ENST00000371079.
- Predominant ROR2 expression is from variant ENST00000375708.
Conclusions:
- ROR1/2 expression in healthy tissues necessitates careful consideration for targeted therapy safety assessments.
- Further research into the function and significance of the predominant ROR1 variant (ENST00000545203) is warranted.
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