Research Papers:

Genetic rearrangements result in altered gene expression and novel fusion transcripts in Sézary syndrome

Katarzyna Iżykowska, Grzegorz K. Przybylski _, Claudia Gand, Floriane C. Braun, Piotr Grabarczyk, Andreas W. Kuss, Karolina Olek-Hrab, Armando N. Bastidas Torres, Maarten H. Vermeer, Willem H. Zoutman, Cornelis P. Tensen and Christian A. Schmidt

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Oncotarget. 2017; 8:39627-39639. https://doi.org/10.18632/oncotarget.17383

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Katarzyna Iżykowska1, Grzegorz K. Przybylski1, Claudia Gand2, Floriane C. Braun2, Piotr Grabarczyk2, Andreas W. Kuss3, Karolina Olek-Hrab4, Armando N. Bastidas Torres5, Maarten H. Vermeer5, Willem H. Zoutman5, Cornelis P. Tensen5, Christian A. Schmidt2

1Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland

2Clinic for Internal Medicine C, University Medicine Greifswald, Greifswald, Germany

3Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany

4Department of Dermatology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland

5Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence to:

Grzegorz K. Przybylski, email: [email protected]

Keywords: Sézary syndrome, NGS, whole genome, RNASeq, rearrangement

Received: July 26, 2016     Accepted: March 27, 2017     Published: April 24, 2017


Sézary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma variant. Molecular pathogenesis of SS is still unclear despite many studies on genetic alterations, gene expression and epigenetic regulations. Through whole genome and transcriptome next generation sequencing nine Sézary syndrome patients were analyzed in terms of copy number variations and rearrangements affecting gene expression. Recurrent copy number variations were detected within 8q (MYC, TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1), but no recurrent rearrangements were identified. However, expression of five genes involved in rearrangements (TMEM244, EHD1, MTMR2, RNF123 and TOX) was altered in all patients. Fifteen rearrangements detected in Sézary syndrome patients and SeAx resulted in an expression of new fusion transcripts, nine of them were in frame (EHD1-CAPN12, TMEM66-BAIAP2, MBD4-PTPRC, PTPRC-CPN2, MYB-MBNL1, TFG-GPR128, MAP4K3-FIGLA, DCP1A-CCL27, MBNL1-KIAA2018) and five resulted in ectopic expression of fragments of genes not expressed in normal T-cells (BAIAP2, CPN2, GPR128, CAPN12, FIGLA). Our results not only underscored the genomic complexity of the Sézary cancer cell genome but also showed an unpreceded large variety of novel gene rearrangements resulting in fusions transcripts and ectopically expressed genes.

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