TY - JOUR
T1 - MicroRNA profiles of t(14;18)-negative follicular lymphoma support a late germinal center B-cell phenotype
AU - Leich, Ellen
AU - Zamo, Alberto
AU - Horn, Heike
AU - Haralambieva, Eugenia
AU - Puppe, Bernhard
AU - Gascoyne, Randy D.
AU - Chan, Wing Chung
AU - Braziel, Rita M.
AU - Rimsza, Lisa M.
AU - Weisenburger, Dennis D.
AU - Delabie, Jan
AU - Jaffe, Elaine S.
AU - Fitzgibbon, Jude
AU - Staudt, Louis M.
AU - Mueller-Hermelink, Hans Konrad
AU - Calaminici, Mariarita
AU - Campo, Elias
AU - Ott, German
AU - Hernández, Luis
AU - Rosenwald, Andreas
PY - 2011/11/17
Y1 - 2011/11/17
N2 - A total of 90% of follicular lymphomas (FLs) harbor the translocation t(14;18) leading to deregulated BCL2 expression. Conversely, 10% of FLs lack the t(14;18), and the majority of these FLs do not express BCL2. The molecular features of t(14;18)-negative FLs remain largely unknown. We performed microRNA expression analysis in 32FLgrades 1 to 3A, including 17 t(14;18)-positive FLs, 9 t(14;18)-negative FLs without BCL2 expression, and 6 t(14;18)-negative FLs with BCL2 expression. MicroRNA profiles were correlated with corresponding mRNA expression patterns, and potential targets were investigated by quantitative PCR and immunohistochemistry in an independent validation series of 83 FLs. Statistical analysis identified 17 microRNAs that were differentially expressed between t(14;18)-positive FLs and t(14;18)-negative FLs. The down-regulation of miR-16, miR-26a, miR-101, miR-29c, and miR138 in the t(14;18)-negative FL subset was associated with profound mRNA expression changes of potential target genes involving cell cycle control, apoptosis, and B-cell differentiation. miR-16 target CHEK1 showed increased expression in t(14;18)-negative FLs, whereas TCL1A expression was reduced, in line with a partial loss of the germinal center B-cell phenotype in this FL subset. In conclusion, t(14;18)-negative FL have distinct microRNA profiles that are associated with an increased proliferative capacity and a "late" germinal center B-cell phenotype.
AB - A total of 90% of follicular lymphomas (FLs) harbor the translocation t(14;18) leading to deregulated BCL2 expression. Conversely, 10% of FLs lack the t(14;18), and the majority of these FLs do not express BCL2. The molecular features of t(14;18)-negative FLs remain largely unknown. We performed microRNA expression analysis in 32FLgrades 1 to 3A, including 17 t(14;18)-positive FLs, 9 t(14;18)-negative FLs without BCL2 expression, and 6 t(14;18)-negative FLs with BCL2 expression. MicroRNA profiles were correlated with corresponding mRNA expression patterns, and potential targets were investigated by quantitative PCR and immunohistochemistry in an independent validation series of 83 FLs. Statistical analysis identified 17 microRNAs that were differentially expressed between t(14;18)-positive FLs and t(14;18)-negative FLs. The down-regulation of miR-16, miR-26a, miR-101, miR-29c, and miR138 in the t(14;18)-negative FL subset was associated with profound mRNA expression changes of potential target genes involving cell cycle control, apoptosis, and B-cell differentiation. miR-16 target CHEK1 showed increased expression in t(14;18)-negative FLs, whereas TCL1A expression was reduced, in line with a partial loss of the germinal center B-cell phenotype in this FL subset. In conclusion, t(14;18)-negative FL have distinct microRNA profiles that are associated with an increased proliferative capacity and a "late" germinal center B-cell phenotype.
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U2 - 10.1182/blood-2011-06-361972
DO - 10.1182/blood-2011-06-361972
M3 - Article
C2 - 21960592
AN - SCOPUS:81555214619
SN - 0006-4971
VL - 118
SP - 5550
EP - 5558
JO - Blood
JF - Blood
IS - 20
ER -