Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLTspecific probes

Author:

Dierlamm Judith1,Baens Mathijs1,Stefanova-Ouzounova Margarita1,Hinz Kristina1,Wlodarska Iwona1,Maes Brigitte1,Steyls Anja1,Driessen Ann1,Verhoef Gregor1,Gaulard Philippe1,Hagemeijer Anne1,Hossfeld Dieter Kurt1,De Wolf-Peeters Christiane1,Marynen Peter1

Affiliation:

1. From the Department of Oncology and Hematology, University Hospital Eppendorf, Hamburg, Germany; the Center for Human Genetics and Flanders Interuniversity Institute for Biotechnology and the Departments of Pathology and Hematology, University of Leuven, Leuven, Belgium; and the Department of Pathology, Centre Hospitalier Universitaire Henri Mondor, Créteil, France.

Abstract

Abstract The translocation of chromosome 11, long arm, region 2, band 1, to chromosome 18, long arm, region 2, band 1 (t(11;18)(q21;q21)) represents a recurrent chromosomal abnormality in extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT) type and leads to a fusion of the apoptosis inhibitor-2 (API2) gene on chromosome 11 and the MALT lymphoma-associated translocation (MLT) gene on chromosome 18. A 2-color fluorescence in situ hybridization (FISH) assay, which can be used for the detection of t(11;18) in interphase nuclei and metaphase chromosomes on fresh and archival tumor tissue, was developed. The P1 artificial chromosome (PAC) clone located immediately telomeric to the MLT gene and the PAC clone spanning the API2 gene were differentially labeled and used to visualize the derivative chromosome 11 resulting from t(11;18), as evident by the overlapping or juxtaposed red and green fluorescent signals. The assay was applied to interphase nuclei of 20 cases with nonmalignant conditions and 122 B-cell non-Hodgkin's lymphomas (NHLs). The latter group comprised 20 cases of nodal follicle center cell lymphoma and diffuse large B-cell NHL, 10 cases of gastric diffuse large B-cell lymphoma, 10 cases of hairy cell leukemia, and 82 cases of MZBCL (41 extranodal from various locations, 19 nodal, and 22 splenic MZBCL) including 35 cases with an abnormal karyotype, 2 of which revealed t(11;18). By interphase FISH, t(11;18) was detected in 8 gastrointestinal low-grade MALT-type lymphomas including the 2 cytogenetically t(11;18)+ cases. In the 8 t(11;18)+ cases, the FISH results were confirmed by reverse transcriptase–polymerase chain reaction (RT-PCR) usingAPI2 and MLT specific primers. Our results indicate that t(11;18)(q21;q21) specifically characterizes a subgroup of low-grade MZBCL of the MALT-type and that the FISH assay described here is a highly specific and rapid test for the detection of this translocation.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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