Recurrent read-through fusion transcripts in breast cancer
- PMID: 24929677
- PMCID: PMC4085473
- DOI: 10.1007/s10549-014-3019-2
Recurrent read-through fusion transcripts in breast cancer
Abstract
Read-through fusion transcripts that result from the splicing of two adjacent genes in the same coding orientation are a recently discovered type of chimeric RNA. We sought to determine if read-through fusion transcripts exist in breast cancer. We performed paired-end RNA-seq of 168 breast samples, including 28 breast cancer cell lines, 42 triple negative breast cancer primary tumors, 42 estrogen receptor positive (ER+) breast cancer primary tumors, and 56 non-malignant breast tissue samples. We analyzed the sequencing data to identify breast cancer associated read-through fusion transcripts. We discovered two recurrent read-through fusion transcripts that were identified in breast cancer cell lines, confirmed across breast cancer primary tumors, and were not detected in normal tissues (SCNN1A-TNFRSF1A and CTSD-IFITM10). Both fusion transcripts use canonical splice sites to join the last splice donor of the 5' gene to the first splice acceptor of the 3' gene, creating an in-frame fusion transcript. Western blots indicated that the fusion transcripts are translated into fusion proteins in breast cancer cells. Custom small interfering RNAs targeting the CTSD-IFITM10 fusion junction reduced expression of the fusion transcript and reduced breast cancer cell proliferation. Read-through fusion transcripts between adjacent genes with different biochemical functions represent a new type of recurrent molecular defect in breast cancer that warrant further investigation as potential biomarkers and therapeutic targets. Both breast cancer associated fusion transcripts identified in this study involve membrane proteins (SCNN1A-TNFRSF1A and CTSD-IFITM10), which raises the possibility that they could be breast cancer-specific cell surface markers.
Figures
Similar articles
-
Detection of redundant fusion transcripts as biomarkers or disease-specific therapeutic targets in breast cancer.Cancer Res. 2012 Apr 15;72(8):1921-8. doi: 10.1158/0008-5472.CAN-11-3142. Epub 2012 Apr 10. Cancer Res. 2012. PMID: 22496456
-
High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: novel fusion partner and splice variants.PLoS One. 2014 Mar 7;9(3):e91264. doi: 10.1371/journal.pone.0091264. eCollection 2014. PLoS One. 2014. PMID: 24608966 Free PMC article.
-
Fusion transcript loci share many genomic features with non-fusion loci.BMC Genomics. 2015 Dec 1;16:1021. doi: 10.1186/s12864-015-2235-4. BMC Genomics. 2015. PMID: 26626734 Free PMC article.
-
Mutation-associated fusion cancer genes in solid tumors.Mol Cancer Ther. 2009 Jun;8(6):1399-408. doi: 10.1158/1535-7163.MCT-09-0135. Epub 2009 Jun 9. Mol Cancer Ther. 2009. PMID: 19509239 Free PMC article. Review.
-
[Fusion genes and transcripts in neoplasia].Mol Biol (Mosk). 2011 Sep-Oct;45(5):793-804. Mol Biol (Mosk). 2011. PMID: 22393775 Review. Russian.
Cited by
-
Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts.Mol Ther Nucleic Acids. 2020 Mar 6;19:1379-1398. doi: 10.1016/j.omtn.2020.01.023. Epub 2020 Jan 29. Mol Ther Nucleic Acids. 2020. PMID: 32160708 Free PMC article.
-
Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer.Front Med (Lausanne). 2023 Aug 31;10:1149860. doi: 10.3389/fmed.2023.1149860. eCollection 2023. Front Med (Lausanne). 2023. PMID: 37727755 Free PMC article.
-
Identification of candidate RNA signatures in triple-negative breast cancer by the construction of a competing endogenous RNA network with integrative analyses of Gene Expression Omnibus and The Cancer Genome Atlas data.Oncol Lett. 2020 Mar;19(3):1915-1927. doi: 10.3892/ol.2020.11292. Epub 2020 Jan 10. Oncol Lett. 2020. PMID: 32194687 Free PMC article.
-
Perspective Insight into Future Potential Fusion Gene Transcript Biomarker Candidates in Breast Cancer.Int J Mol Sci. 2018 Feb 7;19(2):502. doi: 10.3390/ijms19020502. Int J Mol Sci. 2018. PMID: 29414922 Free PMC article. Review.
-
Expression of the MHC Class II Pathway in Triple-Negative Breast Cancer Tumor Cells Is Associated with a Good Prognosis and Infiltrating Lymphocytes.Cancer Immunol Res. 2016 May;4(5):390-9. doi: 10.1158/2326-6066.CIR-15-0243. Epub 2016 Mar 15. Cancer Immunol Res. 2016. PMID: 26980599 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous
