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Do Non-Genomically Encoded Fusion Transcripts Cause Recurrent Chromosomal Translocations?
Institute of Pharmaceutical Biology/ZAFES/DCAL, Goethe-University of Frankfurt, Biocenter, Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany
* Author to whom correspondence should be addressed.
Received: 26 July 2012; in revised form: 14 September 2012 / Accepted: 9 October 2012 / Published: 18 October 2012
(This article belongs to the Special Issue Leukemia
Abstract: We among others have recently demonstrated that normal cells produce “fusion mRNAs”. These fusion mRNAs do not derive from rearranged genomic loci, but rather they are derived from “early-terminated transcripts” (ETTs). Premature transcriptional termination takes place in intronic sequences that belong to “breakpoint cluster regions”. One important property of ETTs is that they exhibit an unsaturated splice donor site. This results in: (1) splicing to “cryptic exons” present in the final intron; (2) Splicing to another transcript of the same gene (intragenic trans-splicing), resulting in “exon repetitions”; (3) splicing to a transcript of another gene (intergenic trans-splicing), leading to “non-genomically encoded fusion transcripts” (NGEFTs). These NGEFTs bear the potential risk to influence DNA repair processes, since they share identical nucleotides with their DNA of origin, and thus, could be used as “guidance RNA” for DNA repair processes. Here, we present experimental data about four other genes. Three of them are associated with hemato-malignancies (ETV6, NUP98 and RUNX1), while one is associated with solid tumors (EWSR1). Our results demonstrate that all genes investigated so far (MLL, AF4, AF9, ENL, ELL, ETV6, NUP98, RUNX1 and EWSR1) display ETTs and produce transpliced mRNA species, indicating that this is a genuine property of translocating genes.
Keywords: recurrent chromosomal translocations; leukemia; solid tumors; genetic rearrangements; RNA-templated DNA repair; premature transcript termination
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Kowarz, E.; Dingermann, T.; Marschalek, R. Do Non-Genomically Encoded Fusion Transcripts Cause Recurrent Chromosomal Translocations? Cancers 2012, 4, 1036-1049.
Kowarz E, Dingermann T, Marschalek R. Do Non-Genomically Encoded Fusion Transcripts Cause Recurrent Chromosomal Translocations? Cancers. 2012; 4(4):1036-1049.
Kowarz, Eric; Dingermann, Theo; Marschalek, Rolf. 2012. "Do Non-Genomically Encoded Fusion Transcripts Cause Recurrent Chromosomal Translocations?" Cancers 4, no. 4: 1036-1049.