Brief Reports |
1 Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency
2 Canadas 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.