Submicroscopic genomic rearrangements change gene expression in T-cell large granular lymphocyte leukemia

Autor:	Christian Schmidt, Piotr Grabarczyk, Mariola Zawada, Robert Weissmann, Wolf-Dieter Ludwig, Karina Nowicka, Grzegorz K. Przybylski, Christoph Busemann, Andreas W. Kuss, Katarzyna Iżykowska
Rok vydání:	2014
Předmět:	Genetics Comparative Genomic Hybridization medicine.diagnostic_test Gene Expression Regulation Leukemic RNA chemical and pharmacologic phenomena Hematology General Medicine Biology Gene Rearrangement T-Lymphocyte Molecular biology DNA sequencing Neoplasm Proteins Leukemia Large Granular Lymphocytic Cell culture Cell Line Tumor Gene expression medicine Humans Gene T-Cell Large Granular Lymphocyte Leukemia In Situ Hybridization Fluorescence Comparative genomic hybridization Fluorescence in situ hybridization
Zdroj:	European journal of haematology. 93(2)
ISSN:	1600-0609
Popis:	Objectives 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.
Databáze:	OpenAIRE
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