Transcriptome profiling uncovers potential common mechanisms in fetal trisomies 18 and 21

Several studies have investigated the gene expression profiles in trisomies 21 and 18 to identify the expression signatures that are characteristic of each of these specific aneuploidy conditions. We hypothesized that the viability of cells with gross genomic imbalances might be associated with the activation of resilience mechanisms that are common to different trisomies and that are reflected by specific shared gene expression patterns. Microarray gene expression analysis of amniocytes from fetuses with trisomy 21 or trisomy 18 was conducted to detect such common expression signatures. Comparative analysis of significantly differentially expressed genes in trisomies 18 and 21 identified 6 dysregulated genes common to both trisomies: OTUD5, ADAMTSL1, TADA2A, PPID, PIAS2, and MAPRE2. These genes are involved in apoptosis, ubiquitination, protein folding, and cell division. Functional analysis demonstrated that both trisomies showed dysregulation of the PI3K/AKT pathway, cell cycle G2/M DNA damage checkpoint regulation, and cell death and survival, as well as inhibition of the upstream regulator TP53. Our data demonstrated that trisomies 18 and 21 share common gene expression signatures, implying that common mechanisms of resilience might be activated in aneuploid cells to resist large genomic imbalances. Studies of other trisomies might further clarify mechanisms activated in trisomy syndromes. Whole genome expression profiling was performed on 19 samples; RNA samples of cultivated amniocytes with trisomy 18 and euploid chromosome constitution were hybridized versus pooled reference RNA. Agilent 4x44 two-color Whole Human Genome Expression arrays (GPL6480), which contain 41,001 probes for interrogation of over 19,644 human genes, were used to estimate global transcriptional alterations in trisomy 18 samples.