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; Stephen Leach; Bruce Woolcock; Ronald J deLeeuw; Ali Bashashati; Laurie H Sehn; Joseph M Connors; Mukesh Chhanabhai; Angela Brooks-Wilson; Randy D Gascoyne

doi:10.3324/haematol.2008.001024

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

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

Authors

Nathalie A Johnson¹, Stephen Leach, Bruce Woolcock, Ronald J deLeeuw, Ali Bashashati, Laurie H Sehn, Joseph M Connors, Mukesh Chhanabhai, Angela Brooks-Wilson, Randy D Gascoyne

Affiliation

¹ Clinical Professor of Pathology, Department of Pathology, British Columbia Cancer Agency, 600 W 10 Avenue, Vancouver, BC, V5Z 4E6, Canada.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / metabolism*
Antibodies, Monoclonal, Murine-Derived
Antigens, CD20 / genetics*
Antigens, CD20 / metabolism
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Binding Sites, Antibody / genetics
Cyclophosphamide / administration & dosage
DNA Mutational Analysis
Doxorubicin / administration & dosage
Drug Resistance, Neoplasm / genetics
Epitopes / genetics
Female
Humans
Immunohistochemistry
Lymphoma, Large B-Cell, Diffuse / drug therapy*
Lymphoma, Large B-Cell, Diffuse / genetics
Lymphoma, Large B-Cell, Diffuse / metabolism
Male
Middle Aged
Molecular Sequence Data
Mutation*
Neoplasm Recurrence, Local
Prednisone / administration & dosage
Rituximab
Vincristine / administration & dosage

Substances

Antibodies, Monoclonal
Antibodies, Monoclonal, Murine-Derived
Antigens, CD20
Epitopes
Rituximab
Vincristine
Doxorubicin
Cyclophosphamide
Prednisone