PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B‐NHL with complex chromosomal rearrangements

We present an extensive characterization of 10 B‐cell lymphomas with a t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was demonstrated by fluorescence in situ hybridization (FISH) using a validated probe set, whereas complex karyotypic changes were reassessed by multiplex‐FISH (M‐FISH). Pathologic and clinical review revealed the presence of this rearrangement in 4 histiocyte‐rich, T‐cell‐rich B‐cell lymphomas (HRTR‐BCLs) and 2 posttransplantation diffuse large B‐cell lymphomas (PTLD‐DLBCLs). In contrast to initial observations describing this translocation in lymphoplasmacytic lymphoma (LPL) and LPL‐derived large B‐cell lymphoma, our data showed a wide morphologic and clinical spectrum associated with the PAX5/IGH rearrangement, pointing to an association between this aberration and a subset of de novo DLBCLs presenting with advanced disease and adverse prognosis. In addition, the recurrent incidence of this rearrangement in both HRTR‐BCL (4 cases) and PTLD‐DLBCL (2 cases) was previously unrecognized and is intriguing. © 2005 Wiley‐Liss, Inc.

[1]  S. Swerdlow,et al.  Lack of PAX5 rearrangements in lymphoplasmacytic lymphomas: reassessing the reported association with t(9;14). , 2004, Human pathology.

[2]  M. Copin,et al.  Three new cases of non-Hodgkin lymphoma with t(9;14)(p13;q32). , 2003, Cancer genetics and cytogenetics.

[3]  J. Salisbury,et al.  Epstein-Barr virus-related post-transplant lymphoproliferative disorder with t(9;14)(p11-12;q32). , 2003, Cancer genetics and cytogenetics.

[4]  F. Speleman,et al.  Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using m‐FISH , 2002, Genes, chromosomes & cancer.

[5]  H. Johnsen,et al.  Detection of illegitimate rearrangement within the immunoglobulin locus on 14q32.3 in B‐cell malignancies using end‐sequenced probes , 2001, Genes, chromosomes & cancer.

[6]  R. Bataille,et al.  Cytogenetic, interphase, and multicolor fluorescence in situ hybridization analyses in primary plasma cell leukemia: a study of 40 patients at diagnosis, on behalf of the Intergroupe Francophone du Myélome and the Groupe Français de Cytogénétique Hématologique. , 2001, Blood.

[7]  G Flandrin,et al.  The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[8]  D. Weisenburger,et al.  Is a duplication of 14q32 a new recurrent chromosomal alteration in B-cell non-Hodgkin lymphoma? , 1999, Cancer genetics and cytogenetics.

[9]  M. Callanan,et al.  Deletion 7q in B-cell low-grade lymphoid malignancies: a cytogenetic/fluorescence in situ hybridization and immunopathologic study. , 1999, Cancer genetics and cytogenetics.

[10]  R. Bataille,et al.  High incidence of cryptic translocations involving the Ig heavy chain gene in multiple myeloma, as shown by fluorescence in situ hybridization , 1999, Genes, chromosomes & cancer.

[11]  S. Mori,et al.  Herpes virus type 8-negative primary effusion lymphoma associated with PAX-5 gene rearrangement and hepatitis C virus: a case report and review of the literature. , 1998, The American journal of surgical pathology.

[12]  H. Ohno,et al.  A case of primary splenic large cell lymphoma with a t(9;14)(p13;q32). , 1998, International journal of hematology.

[13]  M. Busslinger,et al.  Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  E. Wagner,et al.  Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5 BSAP , 1994, Cell.

[15]  F. Speleman,et al.  I;17 translocations and other chromosome 17 rearrangements in human primary neuroblastoma tumors and cell lines , 1994 .

[16]  K Offit,et al.  t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation. , 1992, Blood.

[17]  G. Salles,et al.  Cytogenetic and molecular delineation of a region of chromosome 3q commonly gained in marginal zone B-cell lymphoma. , 2003, Haematologica.

[18]  C. Bastard,et al.  FISH analysis with a YAC probe improves detection of LAZ3/BCL6 rearrangement in non-Hodgkin's lymphoma. , 2000, The hematology journal : the official journal of the European Haematology Association.

[19]  Stephen L. Nutt,et al.  Commitment to the B-lymphoid lineage depends on the transcription factor Pax5 , 1999, Nature.

[20]  R. Dalla‐Favera,et al.  The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. , 1996, Blood.

[21]  F. Speleman,et al.  1;17 translocations and other chromosome 17 rearrangements in human primary neuroblastoma tumors and cell lines. , 1994, Genes, chromosomes & cancer.

[22]  T. Shows,et al.  Molecular analysis of a chromosomal translocation, t(9;14)(p13;q32), in a diffuse large-cell lymphoma cell line expressing the Ki-1 antigen. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Iscn International System for Human Cytogenetic Nomenclature , 1978 .

[24]  S. Rosenberg Validity of the Ann Arbor staging classification for the non-Hodgkin's lymphomas. , 1977, Cancer treatment reports.