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Othman et al. J Cancer Metastasis Treat 2018;4:50 Journal of Cancer
DOI: 10.20517/2394-4722.2018.41 Metastasis and Treatment

Case Report Open Access

Cryptic NUP214-ABL1 fusion with complex
karyotype, episomes and intra-tumor genetic

heterogeneity in a T-cell lymphoblastic lymphoma

Moneeb A.K Othman , Beate Grygalewicz , Agnieszka Kołkowska-Leśniak , Joana B. Melo , Isabel M.
2
1
3
4,5
Carreira , Thomas Liehr 1
4,5
1 Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena D-07740, Germany.
2 Cytogenetic Laboratory, Maria Sklodowska-Curie Memorial Cancer Centre and Institute, Warsaw 02-781, Poland.
3 Department of Lymphatic Diseases, Institute of Hematology and Transfusion, Warsaw 02-776, Poland.
4 Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra 3000-354, Portugal.
5 Centro de Investigac̃ao em Meio Ambiente, Genetica e Oncobiologia (CIMAGO), Coimbra 3001-301, Portugal.
Correspondence to: Dr. Thomas Liehr, Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena
D-07740, Germany. E-mail: Thomas.Liehr@med.uni-jena.de

How to cite this article: Othman MAK, Grygalewicz B, Kołkowska-Leśniak A, Melo JB, Carreira IM, Liehr T. Cryptic NUP214-
ABL1 fusion with complex karyotype, episomes and intra-tumor genetic heterogeneity in a T-cell lymphoblastic lymphoma. J
Cancer Metastasis Treat 2018;4:50. http://dx.doi.org/10.20517/2394-4722.2018.41

Received: 30 Jun 2018 First Decision: 25 Jul 2018 Revised: 26 Jul 2018 Accepted: 2 Aug 2018 Published: 21 Sep 2018

Science Editors: Yi-Hong Zhou Copy Editor: Yuan-Li Wang Production Editor: Huan-Liang Wu

Abstract
T-lymphoblastic lymphoma (T-LBL) is a rare and aggressive form of non-Hodgkin’s lymphoma and little is known
about their molecular background. However, complex karyotypes were already related to this group of malignancy
and associated with poor outcome. Here, we describe a 17-year-old female being diagnosed with T-LBL and a normal
karyotype after standard G-banding with trypsin-Giemsa (GTG)-banding. However, further analyses including high-
resolution molecular approaches, array-comparative genomic hybridization (aCGH), multiplex ligation-dependent
probe amplification, fluorescence in situ hybridization and multicolor chromosome banding revealed a cryptic complex
karyotype, NUP214-ABL1 gene fusion, episomes and intra-tumor genetic heterogeneity. In addition, homozygous loss
of CDKN2A , as well as amplification of oncogene TLX1 (HOX11) were detected. Actually, NUP214-ABL1 fusion gene
replicated autonomously in this case as episomes. Overall, highly amplification of NUP214-ABL1 fusion gene defines
possibly a new subgroup of T-LBL patients which accordingly could benefit from treatment with tyrosine kinase
inhibitors. As episomes are missed in standard karyotyping aCGH should be performed routinely in T-LBL to possibly
detect more of such cases.

Keywords: T-cell lymphoblastic lymphoma, NUP214-ABL1 fusion, complex karyotype, episomes, intra-tumor genetic
heterogeneity, molecular cytogenetics, array comparative genomic hybridization
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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