Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas

I. S. Lossos, C. Y. Okada, R. Tibshirani, R. Warnke, Julie Marie Vose, Timothy Charles Greiner, Ronald Levy

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin's lymphoma (NHL) that is highly heterogeneous from both clinical and histopathologic viewpoints. The immunoglobulin (Ig) heavy (H) chain variable region genes were examined in 71 patients with untreated primary DLBCL. Fifty-eight potentially functional V(H) genes were detected in 53 DLBCL cases; V(H) genes were nonfunctional in 9 cases and were not detected in an additional 9 cases. The use of V(H) gene families by DLBCL tumors was unbiased without overrepresentation of any particular V(H) gene or gene family. Analysis of Ig mutations in comparison to the most closely related germline gene disclosed mutated V(H) genes in all but 1 DLBCL case. More than 2% difference from the most similar germline sequence was detected in 52 potentially functional and the 8 nonfunctional V(H) gene sequences, whereas less than 2% difference from the germline sequence was observed in 3 V(H) gene isolates. Only 3 V(H) gene isolates were unmutated. No correlation was found between V(H) gene use, mutation level, and International Prognostic Index (IPI) or survival. Six of 8 tested tumors showed evidence of ongoing somatic mutations. Evidence for positive or negative antigen selection pressure was observed in 65% of mutated DLBCL cases. Our findings indicate that the etiology and the driving forces for clonal expansion are heterogeneous, which may explain the well-known clinical and pathologic heterogeneity of DLBCL. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)1797-1803
Number of pages7
JournalBlood
Volume95
Issue number5
StatePublished - Mar 1 2000

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Immunoglobulin Genes
Lymphoma, Large B-Cell, Diffuse
Immunoglobulins
Genes
Cells
Mutation
Tumors
Immunoglobulin Heavy Chains
Non-Hodgkin's Lymphoma
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Lossos, I. S., Okada, C. Y., Tibshirani, R., Warnke, R., Vose, J. M., Greiner, T. C., & Levy, R. (2000). Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas. Blood, 95(5), 1797-1803.

Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas. / Lossos, I. S.; Okada, C. Y.; Tibshirani, R.; Warnke, R.; Vose, Julie Marie; Greiner, Timothy Charles; Levy, Ronald.

In: Blood, Vol. 95, No. 5, 01.03.2000, p. 1797-1803.

Research output: Contribution to journalArticle

Lossos, IS, Okada, CY, Tibshirani, R, Warnke, R, Vose, JM, Greiner, TC & Levy, R 2000, 'Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas', Blood, vol. 95, no. 5, pp. 1797-1803.
Lossos IS, Okada CY, Tibshirani R, Warnke R, Vose JM, Greiner TC et al. Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas. Blood. 2000 Mar 1;95(5):1797-1803.
Lossos, I. S. ; Okada, C. Y. ; Tibshirani, R. ; Warnke, R. ; Vose, Julie Marie ; Greiner, Timothy Charles ; Levy, Ronald. / Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas. In: Blood. 2000 ; Vol. 95, No. 5. pp. 1797-1803.
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abstract = "Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin's lymphoma (NHL) that is highly heterogeneous from both clinical and histopathologic viewpoints. The immunoglobulin (Ig) heavy (H) chain variable region genes were examined in 71 patients with untreated primary DLBCL. Fifty-eight potentially functional V(H) genes were detected in 53 DLBCL cases; V(H) genes were nonfunctional in 9 cases and were not detected in an additional 9 cases. The use of V(H) gene families by DLBCL tumors was unbiased without overrepresentation of any particular V(H) gene or gene family. Analysis of Ig mutations in comparison to the most closely related germline gene disclosed mutated V(H) genes in all but 1 DLBCL case. More than 2{\%} difference from the most similar germline sequence was detected in 52 potentially functional and the 8 nonfunctional V(H) gene sequences, whereas less than 2{\%} difference from the germline sequence was observed in 3 V(H) gene isolates. Only 3 V(H) gene isolates were unmutated. No correlation was found between V(H) gene use, mutation level, and International Prognostic Index (IPI) or survival. Six of 8 tested tumors showed evidence of ongoing somatic mutations. Evidence for positive or negative antigen selection pressure was observed in 65{\%} of mutated DLBCL cases. Our findings indicate that the etiology and the driving forces for clonal expansion are heterogeneous, which may explain the well-known clinical and pathologic heterogeneity of DLBCL. (C) 2000 by The American Society of Hematology.",
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