Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas

Izidore Lossos, Ash A. Alizadeh, Michael B. Eisen, Wing C. Chan, Patrick O. Brown, David Botstein, Louis M. Staudt, Ronald Levy

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

B cell diffuse large cell lymphoma (B-DLCL) is a heterogeneous group of tumors, based on significant variations in morphology, clinical presentation, and response to treatment. Gene expression profiling has revealed two distinct tumor subtypes of B-DLCL: germinal center B cell-like DLCL and activated B cell-like DLCL. In a separate study, we determined that B-DLCL can also be subdivided into two groups based on the presence or absence of ongoing Ig gene hypermutation. Here, we evaluated the correlation between these B-DLCL subtypes established by the two different methods. Fourteen primary B-DLCL cases were studied by gene expression profiling using DNA microarrays and for the presence of ongoing mutations in their Ig heavy chain gene. All seven cases classified as germinal center B cell-like DLCL by gene expression showed the presence of ongoing mutations in the Ig genes. Five of the seven cases classified by gene expression as activated B cell-like DLCL had no ongoing somatic mutations, whereas, in the remaining two cases, a single point mutation was observed in only 2 of 15 and 21 examined molecular clones of variable heavy (V(H)) chain gene, respectively. These two cases were distantly related to the rest of the activated B cell-like DLCL tumors by gene expression. Our findings validate the concept that lymphoid malignancies are derived from cells at discrete stages of normal lymphocyte maturation and that the malignant cells retain the genetic program of those normal cells.

Original languageEnglish
Pages (from-to)10209-10213
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number18
StatePublished - Aug 29 2000
Externally publishedYes

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Germinal Center
Lymphoma, Large B-Cell, Diffuse
Immunoglobulins
B-Lymphocytes
Mutation
Immunoglobulin Genes
Gene Expression Profiling
Gene Expression
Neoplasms
Immunoglobulin Heavy Chains
Oligonucleotide Array Sequence Analysis
Point Mutation
Genes
Clone Cells
Lymphocytes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas. / Lossos, Izidore; Alizadeh, Ash A.; Eisen, Michael B.; Chan, Wing C.; Brown, Patrick O.; Botstein, David; Staudt, Louis M.; Levy, Ronald.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 18, 29.08.2000, p. 10209-10213.

Research output: Contribution to journalArticle

Lossos, Izidore ; Alizadeh, Ash A. ; Eisen, Michael B. ; Chan, Wing C. ; Brown, Patrick O. ; Botstein, David ; Staudt, Louis M. ; Levy, Ronald. / Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 18. pp. 10209-10213.
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