Unique morphological spectrum of lymphomas in Nijmegen breakage syndrome (NBS) patients with high frequency of consecutive lymphoma formation
- 31 July 2008
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 216 (3), 337-344
- https://doi.org/10.1002/path.2418
Abstract
Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, radiation hypersensitivity, chromosomal instability and increased incidence of malignancies. In Poland 105 NBS cases showing mutations in the NBS gene (nibrin, NBN), have been diagnosed, ∼53% of which have developed cancer, mainly (>90%) lymphoid malignancies. This study is based upon the largest reported group of NBS-associated lymphomas. The predominant lymphoma types found in these 14 NBS children were diffuse large B cell lymphoma (DLBCL) and T cell lymphoblastic lymphoma (T-LBL/ALL), all showing monoclonal Ig/TCR rearrangements. The spectrum of NBS lymphomas is completely different from sporadic paediatric lymphomas and lymphomas in other immunodeficient patients. Morphological and molecular analysis of consecutive lymphoproliferations in six NBS patients revealed two cases of true secondary lymphoma. Furthermore, 9/13 NBS patients with lymphomas analysed by split-signal FISH showed breaks in the Ig or TCR loci, several of which likely represent chromosome aberrations. The combined data would fit a model in which an NBN gene defect results in a higher frequency of DNA misrejoining during double-strand break (DSB) repair, thereby contributing to an increased likelihood of lymphoma formation in NBS patients. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.This publication has 51 references indexed in Scilit:
- DNA double-strand break and chromosomal rejoining defects with misrejoining in Nijmegen breakage syndrome cellsDNA Repair, 2008
- Molecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCRβ locus rearrangements and putative new T-cell oncogenesLeukemia, 2006
- Two-step activation of ATM by DNA and the Mre11–Rad50–Nbs1 complexNature Structural & Molecular Biology, 2006
- Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cellsNature, 2002
- Diffuse large cell lymphomaCurrent Opinion in Oncology, 2001
- Chromosomal breakage syndromesCurrent Opinion in Immunology, 1999
- Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets Report of the BIOMED-1 CONCERTED ACTION: Investigation of minimal residual disease in acute leukemiaLeukemia, 1999
- Nijmegen breakage syndrome.Journal of Medical Genetics, 1996
- Ataxia Telangiectasia and Lymphoma: An Indication for Individualized Chemotherapy Dosing—Report of Treatment in a Highly Inbred Arab FamilyPediatric Hematology and Oncology, 1995
- Further delineation of the Nijmegen breakage syndromeAmerican Journal of Medical Genetics, 1989