title: Submicroscopic genomic rearrangements change gene expression in T-cell large granular lymphocyte leukemia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Iżykowska
authors.forename: Mariola
authors.initials: M
authors.lastname: Zawada
authors.forename: Karina
authors.initials: K
authors.lastname: Nowicka
authors.forename: Piotr
authors.initials: P
authors.lastname: Grabarczyk
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Kuss
authors.forename: Robert
authors.initials: R
authors.lastname: Weissmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Busemann
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Christian A
authors.initials: CA
authors.lastname: Schmidt
authors.forename: Grzegorz K
authors.initials: GK
authors.lastname: Przybylski
mesh_terms: D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D015973:Gene Expression Regulation, Leukemic; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D054066:Leukemia, Large Granular Lymphocytic / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: Fine-tiling comparative genomic hybridization; RNAseq; T-cell large granular lymphocyte leukemia; fusion transcripts; genomic rearrangements; next-generation sequencing