TY - JOUR
T1 - Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene
AU - Schmidt, Janine
AU - Gong, Shunyou
AU - Marafioti, Teresa
AU - Mankel, Barbara
AU - Gonzalez-Farre, Blanca
AU - Balagué, Olga
AU - Mozos, Ana
AU - Cabeçadas, José
AU - Van Der Walt, Jon
AU - Hoehn, Daniela
AU - Rosenwald, Andreas
AU - Ott, German
AU - Dojcinov, Stefan
AU - Egan, Caoimhe
AU - Nadeu, Ferran
AU - Ramis-Zaldívar, Joan Enric
AU - Clot, Guillem
AU - Bárcena, Carmen
AU - Pérez-Alonso, Vanesa
AU - Endris, Volker
AU - Penzel, Roland
AU - Lome-Maldonado, Carmen
AU - Bonzheim, Irina
AU - Fend, Falko
AU - Campo, Elias
AU - Jaffe, Elaine S.
AU - Salaverria, Itziar
AU - Quintanilla-Martinez, Leticia
N1 - Funding Information:
This work was supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (Miguel Servet contract CP13/00159 and PI15/00580), Generalitat de Catalunya Suport Grups de Recerca (2013-SGR-378), the European Regional Development Fund "Una manera de fer Europa" and the Wilhelm-Sander-Stiftung (2015.058.1; L.Q.-M. and F.F.). This work was partially developed at the Centro Esther Koplowitz, Barcelona, Spain.
Publisher Copyright:
Copyright © 2011 by The American Society of Hematology; all rights reserved.
PY - 2016/8/25
Y1 - 2016/8/25
N2 - Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)-FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)-FL (mean, 0.77 vs 9 copy number alterations per case; P < .001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus wasmore frequently observed in PTFL (40% vs 9%; P 5.075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)-FL displayed a mutational profile similar to t(14;18)+FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)-FL in adults indicate that these are two different disorders.
AB - Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)-FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)-FL (mean, 0.77 vs 9 copy number alterations per case; P < .001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus wasmore frequently observed in PTFL (40% vs 9%; P 5.075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)-FL displayed a mutational profile similar to t(14;18)+FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)-FL in adults indicate that these are two different disorders.
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U2 - 10.1182/blood-2016-03-703819
DO - 10.1182/blood-2016-03-703819
M3 - Article
C2 - 27257180
AN - SCOPUS:84984675232
VL - 128
SP - 1101
EP - 1111
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -