Indications for peripheral light-chain revision and somatic hypermutation without a functional B-cell receptor in precursors of a composite diffuse large B-cell and Hodgkin's lymphoma.
Composite lymphomas are rare combinations of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma in the same patient, where clonal relatedness has been observed in most of the few cases analyzed. Here, we report a composite classical HL and diffuse large B-cell lymphoma (DLBCL) with interesting molecular features. Micromanipulation of single cells and analysis of V gene rearrangements revealed clonal relatedness with shared and distinct mutations, indicative of derivation from a common germinal center (GC) B-cell precursor and also of further development of both lymphomas in a GC. In the DLBCL, a very high mutation load, including inactivating mutations, and two copies of the same clonal rearrangement with different mutations in single cells were observed. Intriguingly, in the DLBCL precursor somatic hypermutation activity continued after acquisition of destructive V gene mutations, a feature previously found only in Epstein-Barr virus (EBV) infected B-cell expansions. Furthermore, we found evidence of light-chain receptor revision in the lymphoma precursor during a GC reaction. Re-expression of the V(D)J recombination machinery may enhance genomic instability in GC B cells and contribute to lymphomagenesis.
Rosenquist
Richard
R
Department of Pathology, University of Frankfurt, Frankfurt, Germany.
Menestrina
Fabio
F
Lestani
Maurizio
M
Küppers
Ralf
R
Hansmann
Martin-Leo
ML
Bräuninger
Andreas
A
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001483:Base Sequence; D002999:Clone Cells; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000032:analysis; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000235:genetics; D006689:Hodgkin Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D004273:DNA, Neoplasm; D007147:Immunoglobulin Light Chains; D011947:Receptors, Antigen, B-Cell; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone