TY - JOUR
T1 - Comparative genomic expression signatures of signal transduction pathways and targets in paediatric Burkitt lymphoma
T2 - a Children's Oncology Group report
AU - Lee, Sanghoon
AU - Day, Nancy S.
AU - Miles, Rodney R.
AU - Perkins, Sherrie L.
AU - Lim, Megan S.
AU - Ayello, Janet
AU - van de Ven, Carmella
AU - Harrison, Lauren
AU - El-Mallawany, Nader K.
AU - Goldman, Stanton
AU - Cairo, Mitchell S.
N1 - Funding Information:
We dedicate this manuscript to Warren G. Sanger, PhD, Human Genetics Laboratories, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, for his contribution of the cytogenetic methods and results. Dr. Sanger, a dedicated physician-scientist, passed away during the final preparation of this manuscript. Additionally, we would like to acknowledge Erin Morris, RN and Virginia Moore, RN, for their assistance in the preparation of this manuscript.
Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2017/5
Y1 - 2017/5
N2 - Burkitt lymphoma (BL) is the most common histological subtype of non-Hodgkin lymphoma (NHL) in children and adolescents. Through the introduction of short intensive multi-agent chemoimmunotherapy, survival has improved significantly over the past 30 years. However, this successful approach is limited by significant chemotherapy-induced acute toxicity and risk of developing resistant disease, demonstrating the need to identify less toxic and targeted therapies. We analysed the comparative genomic signature and targetable signalling pathways in paediatric BL (PEBL) samples from the Children's Oncology Group study (ANHL01P1) by genomic profiling and selected genes were confirmed by quantitative real time polymerase chain reaction. These results were compared to PEBL samples from public databases and utilised the Gene Expression Omnibus (GEO) Series (GSE) 10172 and 4475 (n = 16), and 4732 (n = 15). Three hundred and seventy-six genes (approximately 25%) were similarly expressed among three PEBL sample groups. Several target genes in Toll-like receptor signalling, JAK-STAT signalling and MAPK signalling were significantly overexpressed in PEBL. In addition, several tyrosine kinases, including Bruton tyrosine kinase, protein tyrosine phosphatase and histone deacetylase inhibitor were highly expressed in PEBL. These pre-clinical results suggest that specific signal transduction pathways are overly expressed in PEBL and several pathways could serve as potential future therapeutic targets.
AB - Burkitt lymphoma (BL) is the most common histological subtype of non-Hodgkin lymphoma (NHL) in children and adolescents. Through the introduction of short intensive multi-agent chemoimmunotherapy, survival has improved significantly over the past 30 years. However, this successful approach is limited by significant chemotherapy-induced acute toxicity and risk of developing resistant disease, demonstrating the need to identify less toxic and targeted therapies. We analysed the comparative genomic signature and targetable signalling pathways in paediatric BL (PEBL) samples from the Children's Oncology Group study (ANHL01P1) by genomic profiling and selected genes were confirmed by quantitative real time polymerase chain reaction. These results were compared to PEBL samples from public databases and utilised the Gene Expression Omnibus (GEO) Series (GSE) 10172 and 4475 (n = 16), and 4732 (n = 15). Three hundred and seventy-six genes (approximately 25%) were similarly expressed among three PEBL sample groups. Several target genes in Toll-like receptor signalling, JAK-STAT signalling and MAPK signalling were significantly overexpressed in PEBL. In addition, several tyrosine kinases, including Bruton tyrosine kinase, protein tyrosine phosphatase and histone deacetylase inhibitor were highly expressed in PEBL. These pre-clinical results suggest that specific signal transduction pathways are overly expressed in PEBL and several pathways could serve as potential future therapeutic targets.
KW - gene expression profiles
KW - paediatric Burkitt lymphoma
KW - signal transduction pathways
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U2 - 10.1111/bjh.14604
DO - 10.1111/bjh.14604
M3 - Article
C2 - 28474336
AN - SCOPUS:85018398244
SN - 0007-1048
VL - 177
SP - 601
EP - 611
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -