Back to Search
Start Over
Two Receptors, Two Isoforms, Two Cancers: Comprehensive Analysis of KIT and TrkA Expression in Neuroblastoma and Acute Myeloid Leukemia
- Source :
- Frontiers in Oncology, Vol 9 (2019), Frontiers in Oncology
- Publication Year :
- 2019
- Publisher :
- Frontiers Media S.A., 2019.
-
Abstract
- Pediatric cancers represent a wide variety of different tumors, though they have unique features that distinguish them from adult cancers. Receptor tyrosine kinases KIT and TrkA functions in AML and NB, respectively, are well-characterized. Though expression of these receptors is found in both tumors, little is known about KIT function in NB and TrkA in AML. By combining gene enrichment analysis with multidimensional scaling we showed that pediatric AMLs with t(8;21) or inv16 and high KIT expression levels stand out from other AML subtypes as they share prominent transcriptomic features exclusively with KIT-overexpressing NBs. We showed that AML cell lines had a predominant expression of an alternative TrkAIII isoform, which reportedly has oncogenic features, while NB cell lines had dominating TrkAI-II isoforms. NB cells, on the other hand, had an abnormal ratio of KIT isoforms as opposed to AML cells. Both SCF and NGF exerted protective action against doxorubicin and cytarabine for t(8;21) AML and NB cells. We identified several gene sets both unique and common for pediatric AML and NB, and this expression is associated with KIT or TrkA levels. NMU, DUSP4, RET, SUSD5, NOS1, and GABRA5 genes are differentially expressed in NBs with high KIT expression and are associated with poor survival in NB. We identified HOXA10, BAG3, and MARCKS genes that are connected with TrkA expression and are marker genes of poor outcome in AML. We also report that SLC18A2, PLXNC1, and MRPL33 gene expression is associated with TrkA or KIT expression levels in both AML and NB, and these genes have a prognostic value for both cancers. Thus, we have provided a comprehensive characterization of TrkA and KIT expression along with the oncogenic signatures of these genes across two pediatric tumors.
- Subjects :
- oncogenic signature
0301 basic medicine
Gene isoform
Cancer Research
acute myeloid leukemia
SCF (stem cell factor)
lcsh:RC254-282
Receptor tyrosine kinase
Transcriptome
03 medical and health sciences
neuroblastoma
alternative splicing
0302 clinical medicine
Neuroblastoma
Gene expression
medicine
TrkA (tropomyosin receptor kinase)
Receptor
Gene
Original Research
biology
NGF (nerve growth factor)
Myeloid leukemia
KIT
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
biology.protein
Subjects
Details
- Language :
- English
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....3d1a2bc15f9cc3ca8018041e0ed03bc2