Gene expression and molecular pathway activation signatures of MYCN-amplified neuroblastomasстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 9 ноября 2017 г.
Аннотация:Neuroblastoma is a pediatric cancer arising from sympathetic nervous system.
Remarkable heterogeneity in outcomes is one of its widely known features. One
of the traits strongly associated with the unfavorable subtype is the amplification
of oncogene MYCN. Here, we performed cross-platform biomarker detection
by comparing gene expression and pathway activation patterns from the two
literature reports and from our experimental dataset, combining profiles for the
761 neuroblastoma patients with known MYCN amplification status. We identified
109 / 25 gene expression / pathway activation biomarkers strongly linked with the
MYCN amplification. The marker genes/pathways are involved in the processes of
purine nucleotide biosynthesis, ATP-binding, tetrahydrofolate metabolism, building
mitochondrial matrix, biosynthesis of amino acids, tRNA aminoacylation and NADPlinked
oxidation-reduction processes, as well as in the tyrosine phosphatase activity,
p53 signaling, cell cycle progression and the G1/S and G2/M checkpoints. To connect
molecular functions of the genes involved in MYCN-amplified phenotype, we built a
new molecular pathway using known intracellular protein interaction networks. The
activation of this pathway was highly selective in discriminating MYCN-amplified
neuroblastomas in all three datasets. Our data also suggest that the phosphoinositide
3-kinase (PI3K) inhibitors may provide new opportunities for the treatment of the
MYCN-amplified neuroblastoma subtype.