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

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.

Detection of novel fusion-transcripts by RNA-Seq in T-cell lymphoblastic lymphoma

“…However, this assumption is certainly improbable. This is firstly because it would require an inversion of the genomic structure to place the ARL17A gene downstream KANSL1 , and additionally by the existence of multiple KANSL1-ARIL1A isoforms 13 . Therefore, it is reasonable to think that this fusion results from two steps: first an inversion and subsequently a fusion event between a 5′breakpoint downstream of the KANSL1 exon 3 and a 3′ breakpoint occurring upstream of the ARL17A exon 3 (Fig.…”

Epigenomic, genomic, and transcriptomic landscape of schwannomatosis

“…Another notable fusion is the previously reported cancer predisposition KANSARL fusion between KANSL1 and ARL17A genes on chromosome 17q21.31; however, in similar proportions in SWNTS-SWNs and NS-SWNs (Online Resource Fig. 4) [45].…”

The non‐specific lethal ( NSL ) complex at the crossroads of transcriptional control and cellular homeostasis

“…Among NSL complex members driving cancer traits, mutations in KANSL1 have been reported to promote malignancies. Zhou and co‐workers recently identified a KANSL1‐ARL17A fusion transcript in cancer samples isolated specifically from patients with European ancestry . KANSL1 and ARL17A are neighboring genes on human chromosome 17.…”

“…KANSL1 and ARL17A are neighboring genes on human chromosome 17. The authors found that the KANSL1‐ARL17A fusion is inherited within European populations and could predispose carriers to cancer . In addition, KAT6B‐KANSL1 translocations have been identified in a woman with retroperitoneal leiomyoma , but how the KAT6B‐KANSL1 translocation drives this cancer remains to be identified.…”