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The genomic region encompassing the overlapping SOX11 and Lnc-SOX11-1:1 loci exhibits a complex DNA copy number and mRNA expression pattern

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Abstract
Neuroblastoma (NB) is an aggressive lethal pediatric cancer of the developing sympatho-adrenergic nervous system and characterised by a very low mutation burden while exhibiting highly recurrent DNA copy number alterations. Chromosome 2p gain and more specifically MYCN amplification is observed in most of the high risk cases. Using high-resolution DNA copy number analysis, we identified three NB tumours and two NB cell lines with SOX11 focal amplification. SOX11 is located on 2p25 but independently amplified of MYCN, and a key gene involved in the development of the sympatho-adrenergic lineage and contributing to the NB phenotype as demonstrated by reduced colony formation capacity and induction of G1-S cell cycle arrest upon knock down in NB cells. The SOX11 gene consists of one exon and a very long 3’UTR, targeted by miRNA-204 and miRNA-542-3p, both lower expressed in NB tumours as compared to neuroblasts. Additionally, lnc-SOX11-1:1 is partially overlapping with this 3’UTR and transcribed in sense direction with SOX11. Recently high 3’UTR:CDS ratio’s for neuronal genes and specifically SOX11 were reported, indicating that 3’UTR:CDS ratio can play a role in the development of neuroblastoma. Interestingly, whole genome sequencing of the neuroblastoma CHP-126 cell line revealed a remarkable amplification consisting of the 3’UTR and 5’UTR of SOX11, but excluding the SOX11 exon. Nevertheless, SOX11 mRNA and protein levels were very high while multiple splicing events affecting the 3’UTR were noted. Further analyses are ongoing to explain these enigmatic observations.

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Chicago
Decaesteker, Bieke, Sara De Brouwer, Robrecht Cannoodt, Dries Rombaut, Wouter Van Loocke, Annelies Fieuw, Fanny De Vloed, et al. 2016. “The Genomic Region Encompassing the Overlapping SOX11 and Lnc-SOX11-1:1 Loci Exhibits a Complex DNA Copy Number and mRNA Expression Pattern.” In OncoPoint, 4th Research Seminar, Abstracts, 10–10.
APA
Decaesteker, B., De Brouwer, S., Cannoodt, R., Rombaut, D., Van Loocke, W., Fieuw, A., De Vloed, F., et al. (2016). The genomic region encompassing the overlapping SOX11 and Lnc-SOX11-1:1 loci exhibits a complex DNA copy number and mRNA expression pattern. OncoPoint, 4th Research seminar, Abstracts (pp. 10–10). Presented at the 4th OncoPoint research seminar.
Vancouver
1.
Decaesteker B, De Brouwer S, Cannoodt R, Rombaut D, Van Loocke W, Fieuw A, et al. The genomic region encompassing the overlapping SOX11 and Lnc-SOX11-1:1 loci exhibits a complex DNA copy number and mRNA expression pattern. OncoPoint, 4th Research seminar, Abstracts. 2016. p. 10–10.
MLA
Decaesteker, Bieke, Sara De Brouwer, Robrecht Cannoodt, et al. “The Genomic Region Encompassing the Overlapping SOX11 and Lnc-SOX11-1:1 Loci Exhibits a Complex DNA Copy Number and mRNA Expression Pattern.” OncoPoint, 4th Research Seminar, Abstracts. 2016. 10–10. Print.
@inproceedings{7174333,
  abstract     = {Neuroblastoma (NB) is an aggressive lethal pediatric cancer of the developing sympatho-adrenergic nervous system and characterised by a very low mutation burden while exhibiting highly recurrent DNA copy number alterations. Chromosome 2p gain and more specifically MYCN amplification is observed in most of the high risk cases. Using high-resolution DNA copy number analysis, we identified three NB tumours and two NB cell lines with SOX11 focal amplification. SOX11 is located on 2p25 but independently amplified of MYCN, and a key gene involved in the development of the sympatho-adrenergic lineage and contributing to the NB phenotype as demonstrated by reduced colony formation capacity and induction of G1-S cell cycle arrest upon knock down in NB cells.
The SOX11 gene consists of one exon and a very long 3{\textquoteright}UTR, targeted by miRNA-204 and miRNA-542-3p, both lower expressed in NB tumours as compared to neuroblasts. Additionally, lnc-SOX11-1:1 is partially overlapping with this 3{\textquoteright}UTR and transcribed in sense direction with SOX11. Recently high 3{\textquoteright}UTR:CDS ratio{\textquoteright}s for neuronal genes and specifically SOX11 were reported, indicating that 3{\textquoteright}UTR:CDS ratio can play a role in the development of neuroblastoma.
Interestingly, whole genome sequencing of the neuroblastoma CHP-126 cell line revealed a remarkable amplification consisting of the 3{\textquoteright}UTR and 5{\textquoteright}UTR of SOX11, but excluding the SOX11 exon. Nevertheless, SOX11 mRNA and protein levels were very high while multiple splicing events affecting the 3{\textquoteright}UTR were noted. Further analyses are ongoing to explain these enigmatic observations.},
  author       = {Decaesteker, Bieke and De Brouwer, Sara and Cannoodt, Robrecht and Rombaut, Dries and Van Loocke, Wouter and Fieuw, Annelies and De Vloed, Fanny and Volders, Pieter-Jan and Menten, Bj{\"o}rn and Versteeg, Rogier and Reynolds, Patrick and Hogarty, Michael and Koster, Jan and Speleman, Franki and De Preter, Katleen},
  booktitle    = {OncoPoint, 4th Research seminar, Abstracts},
  language     = {eng},
  location     = {Ghent, Belgium},
  pages        = {10--10},
  title        = {The genomic region encompassing the overlapping SOX11 and Lnc-SOX11-1:1 loci exhibits a complex DNA copy number and mRNA expression pattern},
  year         = {2016},
}