title: CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure.
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.
authors.affiliation: Clinical Professor of Pathology, Department of Pathology, British Columbia Cancer Agency, 600 W 10 Avenue, Vancouver, BC, V5Z 4E6, Canada.
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Stephen
authors.initials: S
authors.lastname: Leach
authors.forename: Bruce
authors.initials: B
authors.lastname: Woolcock
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: deLeeuw
authors.forename: Ali
authors.initials: A
authors.lastname: Bashashati
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Angela
authors.initials: A
authors.lastname: Brooks-Wilson
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001666:Binding Sites, Antibody / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000939:Epitopes; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone