Submicroscopic genomic rearrangements change gene expression in T‐cell large granular lymphocyte leukemia. (9th April 2014)

• Record Type: Journal Article
• Authors: Iżykowska, Katarzyna; Zawada, Mariola; Nowicka, Karina; Grabarczyk, Piotr; Kuss, Andreas W.; Weissmann, Robert; Busemann, Christoph; Ludwig, Wolf‐Dieter; Schmidt, Christian A.; Przybylski, Grzegorz K.
• Is Part Of: European journal of haematology. Volume 93:Number 2(2014:Aug.)
• Page Start: 143
• Page End: 149
• Publication Date: 2014-04-09
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.12318
• Languages: English
• ISSNs: 0902-4441

Abstract

<abstract abstract-type="main" id="ejh12318-abs-0001"> <title>Abstract</title> <sec id="ejh12318-sec-0001" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="ejh12318-sec-0002" sec-type="section"> <title>Methods</title> <p>Multicolor fluorescence <italic>in situ</italic> 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).</p> </sec> <sec id="ejh12318-sec-0003" sec-type="section"> <title>Results</title> <p>Rearrangements were detected within 1p and 2q in MOTN‐1 affecting expression of <italic>FGR, ZEB2, </italic> and <italic>CASP8</italic>, and within 6q in MOTN‐1 and one T‐LGL patient affecting <italic>MAP3K5</italic> and <italic>IFNGR1</italic>. Nineteen genes, among them <italic>FOXN3</italic>, <italic> RIN3, AKT1, PPP2R5C, </italic> were overexpressed as a result of an amplification in 14q in one T‐LGL patient. Two novel fusion transcripts were identified: <italic>CASP8‐ERBB4</italic> in MOTN‐1 and <italic>SBF1‐PKHD1L1</italic> in T‐LGL patient.</p> </sec> <sec id="ejh12318-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>