Iżykowska Katarzyna, Zawada Mariola, Nowicka Karina, Grabarczyk Piotr, Kuss Andreas W, Weissmann Robert, Busemann Christoph, Ludwig Wolf-Dieter, Schmidt Christian A, Przybylski Grzegorz K
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Eur J Haematol. 2014 Aug;93(2):143-9. doi: 10.1111/ejh.12318. Epub 2014 Apr 9.
To better understand the molecular pathogenesis of T-cell large granular lymphocyte leukemia (T-LGL), we decided to search for those genetic alterations in T-LGL patients and MOTN-1 cell line (established from T-LGL patient) that have an impact on gene expression and as a result can influence cell biology.
Multicolor fluorescence in situ hybridization (mFISH) analysis of the MOTN-1 cell line was performed as well as paired-end next-generation sequencing (NGS; Illumina HiSeq2000) of this cell line and one T-LGL patient. In addition, chosen 6q region was characterized in three T-LGL patients using high-resolution comparative genomic hybridization (FT-CGH) and LM-PCR. Gene expression was studied by RNA sequencing (RNAseq; SOLID5500).
Rearrangements were detected within 1p and 2q in MOTN-1 affecting expression of FGR, ZEB2, and CASP8, and within 6q in MOTN-1 and one T-LGL patient affecting MAP3K5 and IFNGR1. Nineteen genes, among them FOXN3, RIN3, AKT1, PPP2R5C, were overexpressed as a result of an amplification in 14q in one T-LGL patient. Two novel fusion transcripts were identified: CASP8-ERBB4 in MOTN-1 and SBF1-PKHD1L1 in T-LGL patient.
This study showed that submicroscopic genomic rearrangements change gene expression in T-LGL. Several genes involved in rearrangements were previously linked to cancer and survival pattern that characterizes T-LGL cells.
