Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte- predominant and classic Hodgkin lymphoma

Arcangelo Liso, Daniela Capello, Teresa Marafioti, Enrico Tiacci, Michaela Cerri, Verena Distler, Marco Paulli, Antonino Carbone, Georges Delsol, Elias Campo, Stefano Pileri, Laura Pasqualucci, Gianluca Gaidano, Brunangelo Falini

Research output: Contribution to journalArticle

Abstract

Aberrant somatic hypermutation (SHM) has been identified as a mechanism for genomewide instability in diffuse large B-cell lymphoma (DLBCL). To assess whether aberrant SHM plays a role in the molecular pathogenesis of Hodgkin lymphoma (HL), we investigated microdissected neoplastic cells of nodular lymphocyte-predominant HL (NLPHL; n = 10) and classic HL (cHL; n = 9) for the presence of mutations in the 5′ sequences of 4 previously identified aberrant SHM targets (PIM1, PAX5, RhoH/TTF, c-MYC). Mutations in one or more genes were detected in 80% of NLPHLs and 55% of cHLs, with 50% and 30% of patients carrying mutations in 2 or more genes, respectively. The most frequently involved protooncogene was PAX5, mutated in 7 of 9 patients with NLPHL and 2 of 9 patients with cHL. In total, 34 mutations were detected in NLPHL (frequency, 1.04/1000 bp) and 35 were detected in patients with cHL (frequency, 1.92/1000 bp). Mutations were of somatic origin because they were absent in control T cells and shared most of the features of the immunoglobulin variable (IGV) gene-associated SHM mechanism - ie, single nucleotide substitutions (n = 63) with rare deletions/insertions (n = 6) and a predominance of transitions over transversions with preferential targeting motifs. Our finding that NLPHL and cHL are targeted by aberrant SHM, as is DLBCL, suggests that these lymphomas may share common molecular pathogenetic events.

Original languageEnglish
Pages (from-to)1013-1020
Number of pages8
JournalBlood
Volume108
Issue number3
DOIs
Publication statusPublished - Aug 1 2006

    Fingerprint

ASJC Scopus subject areas

  • Hematology

Cite this

Liso, A., Capello, D., Marafioti, T., Tiacci, E., Cerri, M., Distler, V., Paulli, M., Carbone, A., Delsol, G., Campo, E., Pileri, S., Pasqualucci, L., Gaidano, G., & Falini, B. (2006). Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte- predominant and classic Hodgkin lymphoma. Blood, 108(3), 1013-1020. https://doi.org/10.1182/blood-2005-10-3949