Identification of CD20 C-terminal deletion mutations associated with loss of CD20 expression in non-Hodgkin's lymphoma.

Abstract

PURPOSE:

Rituximab is commonly incorporated into CD20-positive B-cell lymphoma therapy to improve response and prognosis. With increasing use, resistance to rituximab is a continuing concern, but CD20 mutation as a cause of resistance has not previously been reported.

EXPERIMENTAL DESIGN:

Freshly collected lymphoma cells from 50 patients with previously untreated or relapsed/resistant non-Hodgkin's B-cell lymphomas (diffuse large B cell, n = 22; follicular, n = 7; mucosa associated lymphoid tissue, n = 16; chronic lymphocytic leukemia, n = 2; small lymphocytic lymphoma, n = 1; lymphoplasmacytic, n = 1; mantle cell lymphoma, n = 1) were assessed for CD20 expression by flow cytometry, and CD20 gene sequencing was done on extracted DNA.

RESULTS:

CD20 mutations were found in 11 (22.0%) of 50 patients and could be grouped as C-terminal deletion (8.0%), early termination (10.0%), and extracellular domain (2.0%) or transmembrane domain (2.0%) mutations. The mean fluorescence intensity of CD20 on fresh lymphoma cells was significantly lower for the C-terminal deletion mutation [3.26; 95% confidence interval (95% CI), 0.09-6.89] compared with wild type (30.8; 95% CI, 22.4-39.2; P < 0.05). In contrast, early termination mutations did not show significant differences in CD20 expression compared with wild type (19.5; 95% CI, 10.7-28.4; P > 0.05).

CONCLUSIONS:

It is possible that C-terminal deletion mutations of CD20 may be related to relapse/resistance after rituximab therapy. These mutations should be examined in patients showing progression of disease after partial remission.

• Authors: Yasuhito Terui, Yuji Mishima, Natsuhiko Sugimura, Kiyotsugu Kojima, Takuma Sakurai, Yuko Mishima, Ryoko Kuniyoshi, Akiko Taniyama, Masahiro Yokoyama, Sakura Sakajiri, Kengo Takeuchi, Chie Watanabe, Shunji Takahashi, Yoshinori Ito, Kiyohiko Hatake
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 7 Pg. 2523-30 (Apr 01 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19276251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD20
• Antineoplastic Agents
• Rituximab

Topics

• Amino Acid Sequence
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD20 (chemistry, genetics, metabolism)
• Antineoplastic Agents (therapeutic use)
• Drug Resistance, Neoplasm (genetics)
• Humans
• Lymphoma, B-Cell (drug therapy, genetics, metabolism)
• Molecular Sequence Data
• Rituximab
• Sequence Deletion