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Aneuploidy in Human Oocytes and Preimplantation Embryos
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
The first genome-wide association study (GWAS) to identify common variants that affect aneuploidy in preimplantation embryos has been conducted. Using aneuploidy data from around 46,000 embryos (a mix of day 3 and day 5) from 4700 individuals, McCoy and colleagues found no association with putative maternal meiotic origin and maternal genotypes at the statistical significance threshold used. However, they found that a 600 Kb region (quantitative trait loci, QTL) of low recombination on chromosome 4 that was associated with multiple, complex aneuploidies of mitotic origin (they followed paternal chromosomes, since the meiotic error rate is very low in sperm). The QTL contained common variants of PLK4, a polo-like kinase that regulates centrosome numbers and whose dysregulation can lead to large-scale chromosome missegregation (122,123). Importantly, it was the maternal PLK4 variants that influenced mitotic chromosome segregation, consistent with the model that maternal factors drive the initial mitotic divisions in human preimplantation embryos (58,124,125). Although the QTL contains seven other gene variants, PLK4 is an attractive candidate since it regulates centriole duplication, a critical part of the centrosome cycle, and also mediates spindle formation during the initial cell divisions in mouse and bovine embryos (122,123). Thus, PLK4 variants may cause tripolar spindle formation that results in chaotic karyotypes (Figure 8.11). Importantly, tripolar spindles originating from normally fertilized human embryos have been observed (118).
Clinical utility of microRNAs in renal cell carcinoma: current evidence and future perspectives
Published in Expert Review of Molecular Diagnostics, 2018
Panagiotis Tsiakanikas, Constantinos Giaginis, Christos K. Kontos, Andreas Scorilas
The potential implication of miR-210 in several cellular functions, such as the regulation of HIF network and centrosome cycle, has already been described in previous section [37,40]. The main point in many recent studies has dealt with the significant upregulation of miR-210 in both primary and metastatic RCC [39,62,64,70–72]. However, the currently available studies evaluating the prognostic impact of miR-210 have been rather contradictory. In most of them, RCC patients with high miR-210 expression were at a greater risk of relapsing, presenting also shorter DFS and OS [71,72]. That was more apparent for RCC patients presenting large tumor size [71]. A contrasting study documented that elevated miR-210 expression was associated with favorable clinicopathological features [39]. The observed dissimilarities could be ascribed to the intratumor heterogeneity and the limited number of cases in the latter study, as well as to technical methodological variations, including different normalization techniques and cutoff points.