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. 2009 Mar;94(3):423-7.
doi: 10.3324/haematol.2008.001024. Epub 2009 Feb 11.

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 Johnson  1 , Stephen Leach, Bruce Woolcock, Ronald J deLeeuw, Ali Bashashati, Laurie H Sehn, Joseph M Connors, Mukesh Chhanabhai, Angela Brooks-Wilson, Randy D Gascoyne
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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 Johnson et al. Haematologica. 2009 Mar.

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.

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Figures

Figure 1.
Figure 1.
CD20 expression in a diffuse large B-cell lymphoma sample taken at relapse containing a 4 base pair deletion at nucleotide position 353–356. (A) Representation of the amino acid sequence coding for the trans-membrane portion of the CD20 protein (adapted from Binder et al.) Light blue amino acids are contained within the sequenced region of exon 5 of the MS4A1 gene and dark blue amino acids represent the rituximab epitope brought together by a disulfide bond at two cysteine residues. The red arrow represents the location of the 4 base pair deletion leading to premature termination at amino acid 121 (highlighted with a star). (B) Bright CD20 protein expression by flow cytometry in the mutated sample; inset: CD20 expression of a non-mutated diffuse large B-cell lymphoma sample analyzed during the same time frame demonstrating CD20 fluorescent intensity of benign non-B cells (CD20 negative) and tumor cells (CD20 positive) within the sample. (C) Bright CD20 protein expression by immunohistochemistry in the mutated sample (L26 antibody).
Figure 2.
Figure 2.
Heterogeneous CD20 protein expression by immunohistochemistry in a diffuse large B cell lymphoma sample taken at relapse following R-CHOP therapy
See this image and copyright information in PMC

References

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