Over the last decades, the concept of precision medicine has dramatically renewed the field of medical oncology; the introduction of patient-tailored therapies has significantly improved all measurable outcomes. Liquid biopsy is a revolutionary technique that is opening previously unexpected perspectives. It consists of the detection and isolation of circulating tumor cells, circulating tumor DNA and exosomes, as a source of genomic and proteomic information in patients with cancer. Many technical hurdles have been resolved thanks to newly developed techniques and next-generation sequencing analyses, allowing a broad application of liquid biopsy in a wide range of settings. Initially correlated to prognosis, liquid biopsy data are now being studied for cancer diagnosis, hopefully including screenings, and most importantly for the prediction of response or resistance to given treatments. In particular, the identification of specific mutations in target genes can aid in therapeutic decisions, both in the appropriateness of treatment and in the advanced identification of secondary resistance, aiming to early diagnose disease progression. Still application is far from reality but ongoing research is leading the way to a new era in oncology. This review summarizes the main techniques and applications of liquid biopsy in cancer.

Besides aging, a number of non-modifiable lifestyle-related factors, such as smoking, elevated consumption of caffeine and alcohol, stress, agonist sports, chronic exposure to environmental pollutants, and other nutritional habits exert a negative impact on a women's fertility. In particular, metabolic disorders including diabetes, obesity, and hyperlipidemia commonly associated to hypercaloric diets are suspected to affect a woman's fertility either by direct damage to oocyte health and differentiation, or by indirect interference with the pituitary-hypothalamic axis, resulting in dysfunctional oogenesis. Obese women show decreased insulin sensitivity determining persistent hyperinsulinemia, which may be involved in the pathogenesis of Polycystic Ovary Syndrome. Thus, the reduced insulin secretion induced by dietary adjustments is an attractive non-pharmacological treatment to prevent infertility, and a Mediterranean diet aimed at maintaining normal body mass may be effective in the preservation of ovarian health and physiology. Furthermore, in relation to the oxidative stress as a co-factor of defective oocyte maturation, an appropriate intake of proteins, antioxidants and methyl-donor supplements (1-Carbon Cycle) may decrease the bioavailability of toxic oxidants resulting in the protection of oocyte maturation.

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Bari elements are members of the Tc1-mariner superfamily of DNA transposons, originally discovered in Drosophila melanogaster, and subsequently identified in silico in 11 sequenced Drosophila genomes and as experimentally isolated in four non-sequenced Drosophila species. Bari-like elements have been also studied for their mobility both in vivo and in vitro. We analyzed 23 Drosophila genomes and carried out a detailed characterization of the Bari elements identified, including those from the heterochromatic Bari1 cluster in D. melanogaster. We have annotated 401 copies of Bari elements classified either as putatively autonomous or inactive according to the structure of the terminal sequences and the presence of a complete transposase-coding region. Analyses of the integration sites revealed that Bari transposase prefers AT-rich sequences in which the TA target is cleaved and duplicated. Furthermore evaluation of transposon’s co-occurrence near the integration sites of Bari elements showed a non-random distribution of other transposable elements. We also unveil the existence of a putatively autonomous Bari1 variant characterized by two identical long Terminal Inverted Repeats, in D. rhopaloa. In addition, we detected MITEs related to Bari transposons in 9 species. Phylogenetic analyses based on transposase gene and the terminal sequences confirmed that Bari-like elements are distributed into three subfamilies. A few inconsistencies in Bari phylogenetic tree with respect to the Drosophila species tree could be explained by the occurrence of horizontal transfer events as also suggested by the results of dS analyses. This study further clarifies the Bari transposon’s evolutionary dynamics and increases our understanding on the Tc1-mariner elements’ biology.

SummaryShotgun metagenomics by high-throughput sequencing may allow deep and accurate characterization of host-associated total microbiomes, including bacteria, viruses, protists and fungi. However, the analysis of such sequencing data is still extremely challenging in terms of both overall accuracy and computational efficiency, and current methodologies show substantial variability in misclassification rate and resolution at lower taxonomic ranks or are limited to specific life domains (e.g. only bacteria). We present here MetaShot, a workflow for assessing the total microbiome composition from host-associated shotgun sequence data, and show its overall optimal accuracy performance by analyzing both simulated and real datasets.Availability and Implementation https://github.com/bfosso/MetaShot Supplementary information Supplementary data are available at Bioinformatics online.

Management of localized well-differentiated pancreatic neuroendocrine tumors (panNETs) is controversial and primarily dependent on tumor size. Upfront surgery is usually recommended for tumors larger than 2 cm in diameter since they frequently show metastatic potential, whereas smaller panNETs are generally characterized by an indolent clinical course, with a rate of relapse or metastasis below 15%. To explore whether increased tumor size is paralleled by genomic variations, we compared the rate and the mutational patterns of putative driver genes that are recurrently altered in these tumors by investigating differential cohorts of panNET surgical specimens smaller (n = 27) or larger than 2 cm (n = 29). We found that the cumulative number of mutations detected in panNETs >2 cm was significantly higher (p = 0.03) relative to smaller tumors, while mutations of DAXX were significantly more frequent in the cohort of larger tumors (p = 0.05). Moreover, mutations of DAXX were associated with features of malignancy including increased grade, nodal involvement and lymphovascular invasion, and independently predicted both relapse after surgery (p = 0.05) and reduced DFS in multivariable analysis (p = 0.02). Our data suggest that alterations of the DAXX/ATRX molecular machinery increase the malignant potential of panNETs, and that identification of mutations of DAXX/ATRX in small, nonfunctioning tumors can predict the malignant progression observed in a minority of them.

In the “precision medicine” era, chemotherapy still remains the backbone for the treatment of many cancers, but no affordable predictors of response to the chemodrugs are available in clinical practice. Single nucleotide polymorphisms (SNPs) are gene sequence variations occurring in more than 1% of the full population, and account for approximately 80% of inter-individual genomic heterogeneity. A number of studies have investigated the predictive role of SNPs of genes enrolled in both pharmacodynamics and pharmacokinetics of chemotherapeutics, but the clinical implementation of related results has been modest so far. Among the examined germline polymorphic variants, several SNPs of dihydropyrimidine dehydrogenase (DPYD) and uridine diphosphate glucuronosyltransferases (UGT) have shown a robust role as predictors of toxicity following fluoropyrimidine- and/or irinotecan-based treatments respectively, and a few guidelines are mandatory in their detection before therapy initiation. Contrasting results, however, have been reported on the capability of variants of other genes as MTHFR, TYMS, ERCC1, XRCC1, GSTP1, CYP3A4/3A5 and ABCB1, in predicting either therapy efficacy or toxicity in patients undergoing treatment with pyrimidine antimetabolites, platinum derivatives, irinotecan and taxanes. While formal recommendations for routine testing of these SNPs cannot be drawn at this moment, therapeutic decisions may indeed benefit of germline genomic information, when available. Here, we summarize the clinical impact of germline genomic variants on the efficacy and toxicity of major chemodrugs, with the aim to facilitate the therapeutic expectance of clinicians in the odiern quicksand field of complex molecular biology concepts and controversial trial data interpretation.

Aims Ischaemic heart disease is classically associated with coronary artery disease. Recent evidences showed the correlation between coronary microvascular dysfunction and ischaemic heart disease, even independently of coronary artery disease. Ion channels represent the final effectors of blood flow regulation mechanisms and their genetic variants, in particular of Kir6.2 subunit of the ATP-sensitive potassium channel (KATP), are reported to be involved in ischaemic heart disease susceptibility. The aim of the present study is to evaluate the role of KATP channel and its genetic variants in patients with ischaemic heart disease and evaluate whether differences exist between coronary artery disease and coronary microvascular dysfunction. Methods A total of 603 consecutive patients with indication for coronary angiography due to suspected myocardial ischaemia were enrolled. Patients were divided into three groups: coronary artery disease (G1), coronary microvascular dysfunction (G2) and normal coronary arteries (G3). Analysis of four single nucleotide polymorphisms (rs5215, rs5216, rs5218 and rs5219) of the KCNJ11 gene encoding for Kir6.2 subunit of the KATP channel was performed. Results rs5215 A/A and G/A were significantly more represented in G1, while rs5215 G/G was significantly more represented in G3, rs5216 G/G and C/C were both more represented in G3, rs5218 C/C was more represented in G1 and rs5219 G/A was more represented in G1, while rs5219 G/G was significantly more represented in G2. At multivariate analysis, single nucleotide polymorphism rs5215_G/G seems to represent an ischaemic heart disease independent protective factor. Conclusions These results suggest the potential role of KATP genetic variants in ischaemic heart disease susceptibility, as an independent protective factor. They may lead to a future perspective for gene therapy against ischaemic heart disease.