Published online 11 February 2009
Haematologica, Vol 94, Issue 3, 423-427 doi:10.3324/haematol.2008.001024
Copyright © 2009 by Ferrata Storti Foundation
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Brief Reports

CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure

Nathalie A. Johnson1, Stephen Leach2, Bruce Woolcock1, Ronald J. deLeeuw3, Ali Bashashati3, Laurie H. Sehn4, Joseph M. Connors4, Mukesh Chhanabhai1, Angela Brooks-Wilson2, Randy D. Gascoyne1

1 Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency
2 Canada’s Michael Smith Genome Sciences Centre
3 British Columbia Cancer Research Center and
4 Department of Medical Oncology, British Columbia Cancer Agency and the University of British Columbia, Vancouver, Canada

Correspondence: Randy D. Gascoyne, Clinical Professor of Pathology, Department of Pathology, British Columbia Cancer Agency, 600 W 10th Avenue, Vancouver, BC, V5Z 4E6 Canada. E-mail:rgascoyn{at}bccancer.bc.ca

ABSTRACT

Rituximab binds an epitope on the CD20 antigen, encompassed in exon 5 of the MS4A1 gene. We sequenced this region and correlated the presence of mutations with CD20 protein expression and response to R-CHOP in patients with diffuse large B-cell lymphoma: 264 diagnostic biopsies and 15 biopsies taken at the time of relapse were successfully sequenced. CD20 mutations involving the rituximab epitope were detected in only 1/264 (0.4%) and 1/15 (6%) of the biopsies taken at diagnosis and relapse, respectively. No polymorphic sequence variants were detected in this region. Three patients had malignant cells that were CD20 protein-positive at diagnosis but CD20-negative at relapse. Thus, CD20 mutations involving the rituximab epitope are rare in both de novo and relapsed diffuse large B-cell lymphoma, and do not represent a significant cause of R-CHOP resistance. CD20 protein-negative relapses occur after R-CHOP therapy but their clinical relevance is unknown.

Key words: CD20 antigen, mutation, DLBCL, R-CHOP.