Identification of KANSARL as the first cancer predisposition fusion gene specific to the population of European ancestry origin.

Jeff Xiwu Zhou,Xiaoyan Yang,David D Zhuo,Yanbin Zhang,Ling Wang,Degen Zhuo,Fenghua Yuan,Kesheng Wang,Shunbin Ning,Fengli Li,Liren Tang

doi:10.18632/oncotarget.16385

Jeff Xiwu Zhou, Xiaoyan Yang + Show 9 more

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https://doi.org/10.18632/oncotarget.16385

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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.

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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

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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

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