Apr 9, 2020

Human Transcription Factor and Protein Kinase Gene Fusions in Human Cancer

BioRxiv : the Preprint Server for Biology
K. SalokasMarkku Varjosalo

Abstract

Oncogenic gene fusions are estimated to account for up-to 20 % of cancer morbidity. Originally, oncofusions were identified in blood cancer, but recently multiple sequence-level studies of cancer genomes have established oncofusions throughout all tissue types. However, the functional implications of the identified oncofusions have often not been investigated. In this study, the identified oncofusions from a fusion detection approach (DEEPEST) were analyzed in more detail. In total, DEEPEST contains 28863 unique fusions. From sequence analysis, we found that almost 30% of them (8225) are expected to produce functional fusion proteins with features from both parent genes. Kinases and transcription factors were found to be the main gene families of the protein producing fusions. Considering their role as initiators, actors, and termination points of cellular signaling pathways, we focused our in-depth analyses on them. The domain architecture of the fusions, as well as of their expected interactors, suggests that abnormal molecular context of intact protein domains brought about by fusion events may unlock the oncogenic potential of the wild type counterparts of the fusion proteins. To understand overall effects of oncofusions on...Continue Reading

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Mentioned in this Paper

Archaea
Gene Expression
Fluorescent stain
Codon Genus
Codon (Nucleotide Sequence)
Green Fluorescent Proteins
Structure
Analysis
Retinal Nonattachment, Nonsyndromic Congenital
RNA, Messenger

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