Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Choi Y

PROVIDER: S-EPMC6048111 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Choi Yuri Y Kwon Chae Hwa CH Lee Seon Jin SJ Park Joonghoon J Shin Jong-Yeon JY Park Do Youn DY

British journal of cancer 20180629 2

<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>We validated 24 fusion genes, including novel fusions, by t ...[more]

PMID: 29955133

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Project description:BackgroundColorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Recent studies have observed causative mutations in susceptible genes related to colorectal cancer in 10 to 15% of the patients. This highlights the importance of identifying mutations for early detection of this cancer for more effective treatments among high risk individuals. Mutation is considered as the key point in cancer research. Many studies have performed cancer subtyping based on the type of frequently mutated genes, or the proportion of mutational processes. However, to the best of our knowledge, combination of these features has never been used together for this task. This highlights the potential to introduce better and more inclusive subtype classification approaches using wider range of related features to enable biomarker discovery and thus inform drug development for CRC.ResultsIn this study, we develop a new pipeline based on a novel concept called 'gene-motif', which merges mutated gene information with tri-nucleotide motif of mutated sites, for colorectal cancer subtype identification. We apply our pipeline to the International Cancer Genome Consortium (ICGC) CRC samples and identify, for the first time, 3131 gene-motif combinations that are significantly mutated in 536 ICGC colorectal cancer samples. Using these features, we identify seven CRC subtypes with distinguishable phenotypes and biomarkers, including unique cancer related signaling pathways, in which for most of them targeted treatment options are currently available. Interestingly, we also identify several genes that are mutated in multiple subtypes but with unique sequence contexts.ConclusionOur results highlight the importance of considering both the mutation type and mutated genes in identification of cancer subtypes and cancer biomarkers. The new CRC subtypes presented in this study demonstrates distinguished phenotypic properties which can be effectively used to develop new treatments. By knowing the genes and phenotypes associated with the subtypes, a personalized treatment plan can be developed that considers the specific phenotypes associated with their genomic lesion.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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