Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling

Karen E. Deffenbacher, Javeed Iqbal, Warren Sanger, Yulei Shen, Cynthia Lachel, Zhongfeng Liu, Yanyan Liu, Megan S. Lim, Sherrie L. Perkins, Kai Fu, Lynette M Smith, James Lynch, Louis M. Staudt, Lisa M. Rimsza, Elaine Jaffe, Andreas Rosenwald, German K. Ott, Jan Delabie, Elias Campo, Randy D. Gascoyne & 5 others Mitchell S. Cairo, Dennis D. Weisenburger, Timothy Charles Greiner, Thomas G. Gross, Wing C. Chan

Research output: Contribution to journalArticle

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Abstract

Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell lymphoma. We observed frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31% (5 of 16) and gain or amplification in 50% (6 of 12) nonrearranged cases. MYC rearrangement was present in 96% (23 of 24) BL cases. Array-based CGH analysis identified abnormalities that are shared between adult and pediatric DLBCL (+12q15, +19q13, -6q), and abnormalities unique to the pediatric cases (-4p14, -19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age. Elucidation of the underlying target genes may provide insight into factors that modulate outcome and could provide potential novel therapeutic targets with less toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.

Original languageEnglish (US)
Pages (from-to)3757-3766
Number of pages10
JournalBlood
Volume119
Issue number16
DOIs
StatePublished - Apr 19 2012

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Pediatrics
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Lymphoma, Large B-Cell, Diffuse
Cells
Burkitt Lymphoma
Gene Expression Profiling
Gene expression
B-Lymphocytes
Germinal Center
MicroRNAs
Amplification
Toxicity
Tumors
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling. / Deffenbacher, Karen E.; Iqbal, Javeed; Sanger, Warren; Shen, Yulei; Lachel, Cynthia; Liu, Zhongfeng; Liu, Yanyan; Lim, Megan S.; Perkins, Sherrie L.; Fu, Kai; Smith, Lynette M; Lynch, James; Staudt, Louis M.; Rimsza, Lisa M.; Jaffe, Elaine; Rosenwald, Andreas; Ott, German K.; Delabie, Jan; Campo, Elias; Gascoyne, Randy D.; Cairo, Mitchell S.; Weisenburger, Dennis D.; Greiner, Timothy Charles; Gross, Thomas G.; Chan, Wing C.

In: Blood, Vol. 119, No. 16, 19.04.2012, p. 3757-3766.

Research output: Contribution to journalArticle

Deffenbacher, KE, Iqbal, J, Sanger, W, Shen, Y, Lachel, C, Liu, Z, Liu, Y, Lim, MS, Perkins, SL, Fu, K, Smith, LM, Lynch, J, Staudt, LM, Rimsza, LM, Jaffe, E, Rosenwald, A, Ott, GK, Delabie, J, Campo, E, Gascoyne, RD, Cairo, MS, Weisenburger, DD, Greiner, TC, Gross, TG & Chan, WC 2012, 'Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling', Blood, vol. 119, no. 16, pp. 3757-3766. https://doi.org/10.1182/blood-2011-05-349662
Deffenbacher, Karen E. ; Iqbal, Javeed ; Sanger, Warren ; Shen, Yulei ; Lachel, Cynthia ; Liu, Zhongfeng ; Liu, Yanyan ; Lim, Megan S. ; Perkins, Sherrie L. ; Fu, Kai ; Smith, Lynette M ; Lynch, James ; Staudt, Louis M. ; Rimsza, Lisa M. ; Jaffe, Elaine ; Rosenwald, Andreas ; Ott, German K. ; Delabie, Jan ; Campo, Elias ; Gascoyne, Randy D. ; Cairo, Mitchell S. ; Weisenburger, Dennis D. ; Greiner, Timothy Charles ; Gross, Thomas G. ; Chan, Wing C. / Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling. In: Blood. 2012 ; Vol. 119, No. 16. pp. 3757-3766.
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abstract = "Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell lymphoma. We observed frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31{\%} (5 of 16) and gain or amplification in 50{\%} (6 of 12) nonrearranged cases. MYC rearrangement was present in 96{\%} (23 of 24) BL cases. Array-based CGH analysis identified abnormalities that are shared between adult and pediatric DLBCL (+12q15, +19q13, -6q), and abnormalities unique to the pediatric cases (-4p14, -19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age. Elucidation of the underlying target genes may provide insight into factors that modulate outcome and could provide potential novel therapeutic targets with less toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.",
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AU - Deffenbacher, Karen E.

AU - Iqbal, Javeed

AU - Sanger, Warren

AU - Shen, Yulei

AU - Lachel, Cynthia

AU - Liu, Zhongfeng

AU - Liu, Yanyan

AU - Lim, Megan S.

AU - Perkins, Sherrie L.

AU - Fu, Kai

AU - Smith, Lynette M

AU - Lynch, James

AU - Staudt, Louis M.

AU - Rimsza, Lisa M.

AU - Jaffe, Elaine

AU - Rosenwald, Andreas

AU - Ott, German K.

AU - Delabie, Jan

AU - Campo, Elias

AU - Gascoyne, Randy D.

AU - Cairo, Mitchell S.

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy Charles

AU - Gross, Thomas G.

AU - Chan, Wing C.

PY - 2012/4/19

Y1 - 2012/4/19

N2 - Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell lymphoma. We observed frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31% (5 of 16) and gain or amplification in 50% (6 of 12) nonrearranged cases. MYC rearrangement was present in 96% (23 of 24) BL cases. Array-based CGH analysis identified abnormalities that are shared between adult and pediatric DLBCL (+12q15, +19q13, -6q), and abnormalities unique to the pediatric cases (-4p14, -19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age. Elucidation of the underlying target genes may provide insight into factors that modulate outcome and could provide potential novel therapeutic targets with less toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.

AB - Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell lymphoma. We observed frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31% (5 of 16) and gain or amplification in 50% (6 of 12) nonrearranged cases. MYC rearrangement was present in 96% (23 of 24) BL cases. Array-based CGH analysis identified abnormalities that are shared between adult and pediatric DLBCL (+12q15, +19q13, -6q), and abnormalities unique to the pediatric cases (-4p14, -19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age. Elucidation of the underlying target genes may provide insight into factors that modulate outcome and could provide potential novel therapeutic targets with less toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.

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