Abstract
Gene fusion is one of the hallmarks of cancer. Recent advances in RNA-seq of cancer transcriptomes have facilitated the discovery of fusion transcripts. In this study, we report identification of a surprisingly large number of fusion transcripts, including six KANSARL (KANSL1-ARL17A) transcripts that resulted from the fusion between the KANSL1 and ARL17A genes using a RNA splicingcode model. Five of these six KANSARL fusion transcripts are novel. By systematic analysis of RNA-seq data of glioblastoma, prostate cancer, lung cancer, breast cancer, and lymphoma from different regions of the World, we have found that KANSARL fusion transcripts were rarely detected in the tumors of individuals from Asia or Africa. In contrast, they exist in 30 - 52% of the tumors from North Americans cancer patients. Analysis of CEPH/Utah Pedigree 1463 has revealed that KANSARL is a familially-inherited fusion gene. Further analysis of RNA-seq datasets of the 1000 Genome Project has indicated that KANSARL fusion gene is specific to 28.9% of the population of European ancestry origin. In summary, we demonstrated that KANSARL is the first cancer predisposition fusion gene associated with genetic backgrounds of European ancestry origin.
Highlights
Genetic predisposition to cancer has been well known for several centuries initially through observation of unusual familial clusterings, and later through identification of cancerprone families that demonstrate Mendelian inheritance of cancer predisposition using different traditional techniques such as comparative genomic hybridization [1,2,3,4]
We report identification of a surprisingly large number of fusion transcripts, including six KANSARL (KANSL1-ARL17A) transcripts that resulted from the fusion between the KANSL1 and ARL17A genes using a RNA splicingcode model
By systematic analysis of RNA-seq data of glioblastoma, prostate cancer, lung cancer, breast cancer, and lymphoma from different regions of the World, we have found that KANSARL fusion transcripts were rarely detected in the tumors of individuals from Asia or Africa
Summary
Genetic predisposition to cancer has been well known for several centuries initially through observation of unusual familial clusterings, and later through identification of cancerprone families that demonstrate Mendelian inheritance of cancer predisposition using different traditional techniques such as comparative genomic hybridization [1,2,3,4]. Over 100 cancer predisposition genes (CPGs) have been identified, including BRCA1 and BRCA2 in breast cancer, TP53 in Li–Fraumeni syndrome, and APC in familial adenomatous polyposis [1]. All these CPGs are derived from known genes carrying point mutations; none of them are derived from gene fusion [1]. Its fusion junction has turned out to be identical to a cDNA clone [34] Details about this fusion that of transcript remain to be elusive, including its expression patterns, relationship to somatic and germline mutations, and association with cancer types and genetic backgrounds
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
