Integrative analysis of oncogenic fusion genes and their functional impact in colorectal cancer

Background Fusion genes are good candidates of molecular targets for cancer therapy. However, there is insufficient research on the clinical implications and functional characteristics of fusion genes in colorectal cancer (CRC). Methods In this study, we analysed RNA sequencing data of CRC patients...

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Published inBritish journal of cancer Vol. 119; no. 2; pp. 230 - 240
Main Authors Choi, Yuri, Kwon, Chae Hwa, Lee, Seon Jin, Park, Joonghoon, Shin, Jong-Yeon, Park, Do Youn
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 17.07.2018
Nature Publishing Group
Subjects
631/67/1857
631/67/69
692/699/1503/1504/1885/1393
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell fusion
Cell lines
Cell migration
Cell proliferation
Colorectal cancer
Colorectal carcinoma
Data processing
Drug Resistance
Epidemiology
Gene expression
Genes
Molecular chains
Molecular Medicine
Oncology
Precision medicine
Ribonucleic acid
RNA
Tumors
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Summary:Background Fusion genes are good candidates of molecular targets for cancer therapy. However, there is insufficient research on the clinical implications and functional characteristics of fusion genes in colorectal cancer (CRC). Methods In this study, we analysed RNA sequencing data of CRC patients (147 tumour and 47 matched normal tissues) to identify oncogenic fusion genes and evaluated their role in CRC. Results We validated 24 fusion genes, including novel fusions, by three algorithms and Sanger sequencing. Fusions from most patients were mutually exclusive CRC oncogenes and included tumour suppressor gene mutations. Eleven fusion genes from 13 patients (8.8%) were determined as oncogenic fusion genes by analysing their gene expression and function. To investigate their oncogenic impact, we performed proliferation and migration assays of CRC cell lines expressing fusion genes of GTF3A - CDK8 , NAGLU- IKZF3 , RNF121- FOLR2 , and STRN-ALK . Overexpression of these fusion genes increased cell proliferation except GTF3A-CDK8 . In addition, overexpression of NAGLU-IKZF3 enhanced migration of CRC cells. We demonstrated that NAGLU-IKZF3 , RNF121-FOLR2 , and STRN-ALK had tumourigenic effects in CRC. Conclusion In summary, we identified and characterised oncogenic fusion genes and their function in CRC, and implicated NAGLU-IKZF3 and RNF121-FOLR2 as novel molecular targets for personalised medicine development.
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ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-018-0153-3