Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations

Ellen Leich, Itziar Salaverria, Silvia Bea, Andreas Zettl, George Wright, Victor Moreno, Randy D. Gascoyne, Wing Chung Chan, Rita Braziel, Lisa M. Rimsza, Dennis D. Weisenburger, Jan Delabie, Elaine S. Jaffe, Andrew Lister, Jude Fitzgibbon, Louis M. Staudt, Elena M. Hartmann, Hans Konrad Mueller-Hermelink, Elias Campo, German OttAndreas Rosenwald

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32; q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. Acomparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14;18)-positive FL, whereas activated B cell-like, NFκB, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14;18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.

Original languageEnglish (US)
Pages (from-to)826-834
Number of pages9
JournalBlood
Volume114
Issue number4
DOIs
StatePublished - 2009

Fingerprint

Follicular Lymphoma
Transcriptome
Gene expression
Cells
Polymorphism
Amplification
Nucleotides
Genes
B-Lymphocytes
Genetic Translocation
Germinal Center
Comparative Genomic Hybridization
Gene Amplification
Single Nucleotide Polymorphism
Molecular Biology
Immunohistochemistry
Cell Proliferation
Gene Expression

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Leich, E., Salaverria, I., Bea, S., Zettl, A., Wright, G., Moreno, V., ... Rosenwald, A. (2009). Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood, 114(4), 826-834. https://doi.org/10.1182/blood-2009-01-198580

Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. / Leich, Ellen; Salaverria, Itziar; Bea, Silvia; Zettl, Andreas; Wright, George; Moreno, Victor; Gascoyne, Randy D.; Chan, Wing Chung; Braziel, Rita; Rimsza, Lisa M.; Weisenburger, Dennis D.; Delabie, Jan; Jaffe, Elaine S.; Lister, Andrew; Fitzgibbon, Jude; Staudt, Louis M.; Hartmann, Elena M.; Mueller-Hermelink, Hans Konrad; Campo, Elias; Ott, German; Rosenwald, Andreas.

In: Blood, Vol. 114, No. 4, 2009, p. 826-834.

Research output: Contribution to journalArticle

Leich, E, Salaverria, I, Bea, S, Zettl, A, Wright, G, Moreno, V, Gascoyne, RD, Chan, WC, Braziel, R, Rimsza, LM, Weisenburger, DD, Delabie, J, Jaffe, ES, Lister, A, Fitzgibbon, J, Staudt, LM, Hartmann, EM, Mueller-Hermelink, HK, Campo, E, Ott, G & Rosenwald, A 2009, 'Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations', Blood, vol. 114, no. 4, pp. 826-834. https://doi.org/10.1182/blood-2009-01-198580
Leich, Ellen ; Salaverria, Itziar ; Bea, Silvia ; Zettl, Andreas ; Wright, George ; Moreno, Victor ; Gascoyne, Randy D. ; Chan, Wing Chung ; Braziel, Rita ; Rimsza, Lisa M. ; Weisenburger, Dennis D. ; Delabie, Jan ; Jaffe, Elaine S. ; Lister, Andrew ; Fitzgibbon, Jude ; Staudt, Louis M. ; Hartmann, Elena M. ; Mueller-Hermelink, Hans Konrad ; Campo, Elias ; Ott, German ; Rosenwald, Andreas. / Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. In: Blood. 2009 ; Vol. 114, No. 4. pp. 826-834.
@article{62616e68e95343bda342aa9039e8678f,
title = "Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations",
abstract = "Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32; q21) chromosomal translocation in approximately 90{\%} of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. Acomparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14;18)-positive FL, whereas activated B cell-like, NFκB, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32{\%} of t(14;18)-negative FLs showed weak or absent CD10 expression and 91{\%} an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.",
author = "Ellen Leich and Itziar Salaverria and Silvia Bea and Andreas Zettl and George Wright and Victor Moreno and Gascoyne, {Randy D.} and Chan, {Wing Chung} and Rita Braziel and Rimsza, {Lisa M.} and Weisenburger, {Dennis D.} and Jan Delabie and Jaffe, {Elaine S.} and Andrew Lister and Jude Fitzgibbon and Staudt, {Louis M.} and Hartmann, {Elena M.} and Mueller-Hermelink, {Hans Konrad} and Elias Campo and German Ott and Andreas Rosenwald",
year = "2009",
doi = "10.1182/blood-2009-01-198580",
language = "English (US)",
volume = "114",
pages = "826--834",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "4",

}

TY - JOUR

T1 - Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations

AU - Leich, Ellen

AU - Salaverria, Itziar

AU - Bea, Silvia

AU - Zettl, Andreas

AU - Wright, George

AU - Moreno, Victor

AU - Gascoyne, Randy D.

AU - Chan, Wing Chung

AU - Braziel, Rita

AU - Rimsza, Lisa M.

AU - Weisenburger, Dennis D.

AU - Delabie, Jan

AU - Jaffe, Elaine S.

AU - Lister, Andrew

AU - Fitzgibbon, Jude

AU - Staudt, Louis M.

AU - Hartmann, Elena M.

AU - Mueller-Hermelink, Hans Konrad

AU - Campo, Elias

AU - Ott, German

AU - Rosenwald, Andreas

PY - 2009

Y1 - 2009

N2 - Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32; q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. Acomparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14;18)-positive FL, whereas activated B cell-like, NFκB, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14;18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.

AB - Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32; q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. Acomparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14;18)-positive FL, whereas activated B cell-like, NFκB, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14;18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.

UR - http://www.scopus.com/inward/record.url?scp=68249137273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68249137273&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-01-198580

DO - 10.1182/blood-2009-01-198580

M3 - Article

C2 - 19471018

AN - SCOPUS:68249137273

VL - 114

SP - 826

EP - 834

JO - Blood

JF - Blood

SN - 0006-4971

IS - 4

ER -