Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations.
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. A comparison 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, NFkappaB, 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.
Leich
Ellen
E
Institute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg, Germany.
Salaverria
Itziar
I
Bea
Silvia
S
Zettl
Andreas
A
Wright
George
G
Moreno
Victor
V
Gascoyne
Randy D
RD
Chan
Wing-Chung
WC
Braziel
Rita M
RM
Rimsza
Lisa M
LM
Weisenburger
Dennis D
DD
Delabie
Jan
J
Jaffe
Elaine S
ES
Lister
Andrew
A
Fitzgibbon
Jude
J
Staudt
Louis M
LM
Hartmann
Elena M
EM
Mueller-Hermelink
Hans-Konrad
HK
Campo
Elias
E
Ott
German
G
Rosenwald
Andreas
A
D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D005784:Gene Amplification / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic
D019253:Proto-Oncogene Proteins c-bcl-2