Distribution and pattern of BCL-6 mutations throughout the spectrum of B-cell neoplasia

Daniela Capello, Umberto Vitolo, Laura Pasqualucci, Silvia Quattrone, Giuseppe Migliaretti, Lucia Fassone, Cristiano Ariatti, Daniela Vivenza, Annunziata Gloghini, Cristina Pastore, Carlo Lanza, Josep Nomdedeu, Barbara Botto, Roberto Freilone, Daniela Buonaiuto, Vittorina Zagonel, Eugenio Gallo, Giorgio Palestro, Giuseppe Saglio, Riccardo Dalla-FaveraAntonino Carbone, Gianluca Gaidano

Research output: Contribution to journalArticlepeer-review

Abstract

BCL-6 mutations are accumulated during B-cell transit through the germinal center (GC) and provide a histogenetic marker for B-cell tumors. On the basis of a comprehensive analysis of 308 B-cell neoplasms, we (1) expand the spectrum of tumors associated with BCL-6 mutations; (2) corroborate the notion that mutations cluster with GC and post-GC B-cell neoplasms; and (3) identify heterogeneous mutation frequency among B-lineage diffuse large cell lymphoma (B-DLCL) subsets. Mutations are virtually absent in acute lymphoblastic leukemia (P <.001) and mantle cell lymphoma (P <.05), whereas they occur frequently in GC or post-GC neoplasms, including lymphoplasmacytoid lymphoma, follicular lymphoma, MALT lymphomas, B-DLCL and Burkitt lymphoma. Among B-DLCL mutations occur frequently in systemic nodal B-DLCL, primary extranodal B-DLCL, CD5+ B-DLCL, CD30+ B-DLCL, and primary splenic B-DLCL, suggesting a similar histogenesis of these B-DLCL subsets. Conversely, mutations are rare in primary mediastinal B-DLCL with sclerosis (10.0%; P <.01), supporting a distinct histogenesis for this lymphoma. Longitudinal follow-up of B-DLCL transformed from follicular lymphoma shows that they BCL-6 mutations may accumulate during histologic progression. Mutations also occur in some B-cell chronic lymphocytic leukemias, small lymphocytic lymphomas, and hairy cell leukemias, consistent with the hypothesis that a fraction of these lymphoproliferations are related to GC- like cells. Finally, the molecular pattern of 193 mutational events reinforces the hypothesis that mutations of BCL-6 and immunoglobulin genes are caused by similar mechanisms.

Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalBlood
Volume95
Issue number2
Publication statusPublished - Jan 15 2000

ASJC Scopus subject areas

  • Hematology

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