Identification of a putative transcriptome signature common to neuroblastoma and neural crest cells

Abstract

Neuroblastoma, the most common extracranial tumor in children, is caused by genetic lesions in neural crest precursors of the peripheral nervous system. However, since neural crest cells are neither present after birth and nor are they readily accessible for analysis, very little is known about the genetic networks they might share with neuroblastoma cells during their development, despite their common embryonic origin. Here we have developed a novel resource for lineage tracing and for the isolation of neural crest cells in the chick embryo, enabling us to perform a genome-wide expression screen in neural crest progenitors. In this analysis, we efficiently retrieved known neural crest specific genes that validate our screening strategy and we identified new genes that participate in diverse cell activities, yet with a strong representation of genes associated to cell signaling and cell mobility, two hallmarks of migratory cells. We crossed this transcriptome data with that in the neuroblastoma gene server to search for the human orthologues of these genes associated with neuroblastoma. Accordingly, we retrieved 54 genes expressed strongly in both populations, from which we were able to validate a total of 27 genes expressed in the neural crest that are relevant to neuroblastoma formation. We propose that neural crest and neuroblastoma tumor cells share a common genetic signature that might serve to characterize neuroblastoma cancer stem cells, thereby contributing to the identification of specific targets against which new therapeutic strategies can be designed.

Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways

“…Of these, 11 were differentially expressed between MRT subgroups 1 and 2 (FDR < 0.05). 10 of the 11 genes were over-expressed in subgroup 1 (Table S4), including genes linked to neuronal differentiation (e.g., BEX1 , FAM5C/BRINP3; Coyle et al, 2011; Terashima et al, 2010; Vilar et al, 2006) or neural crest differentiation (e.g., ENC1; Rabadán et al, 2013). Conversely, of the 92 genes reported (Grupenmacher et al, 2013) as over-expressed in RTK relative to AT/RT, 21 were differentially expressed between sub-group 1 and 2, and all were over-expressed in sub-group 2 (one-sided Fisher’s exact p value = 1.193e-13; Table S4).…”

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates

“…Besides WE transcriptome analyses, previous genome-wide gene expression studies in vertebrates using low-input RNA sequencing have focused on cleavage, gastrulation, or early organogenesis [ 5 , 7 , 8 , 11 , 79 , 80 ]. At the end of neurulation in particular, transcriptome of definitive NC cells has been obtained just prior to or during their migration [ 81 – 83 ]. Other studies have taken advantage of naive ectoderm reprogrammed in vitro into different ectoderm cell fates such as neural, NC, or placodes cells [ 10 , 84 – 87 ].…”

Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier

“…Jensen et al (2015) showed that metastatic NB was characterized with an increased expression of CD44 marker, compared to non-metastatic controls. Nonetheless, the lack of CD44 expression was associated with aggressive and metastatic behavior, as well as unfavorable outcomes (Munchar et al, 2003; Siapati et al, 2011; Rabadan et al, 2013; Nardella et al, 2015). CD44 is involved in cell-cell adhesion, promoting an antagonistic role vis-a-vis cancer metastasis: its downregulation is thought to be necessary in NB for the cells to acquire a metastatic potential (Rabadan et al, 2013).…”

“…Nonetheless, the lack of CD44 expression was associated with aggressive and metastatic behavior, as well as unfavorable outcomes (Munchar et al, 2003; Siapati et al, 2011; Rabadan et al, 2013; Nardella et al, 2015). CD44 is involved in cell-cell adhesion, promoting an antagonistic role vis-a-vis cancer metastasis: its downregulation is thought to be necessary in NB for the cells to acquire a metastatic potential (Rabadan et al, 2013). This was further supported with retrospective studies showing a correlation between increased expression of CD44 and favorable tumors on histology (Munchar et al, 2003).…”