Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition.

Background: There is an ongoing research for breast cancer diagnostic tools that are cheaper, more accurate and more convenient than mammography. Methods: In this study, we employed surface-enhanced Raman scattering (SERS) for analysing urine from n = 53 breast cancer patients and n = 22 controls, with the aim of discriminating between the two groups using multivariate data analysis techniques such as principal component analysis—linear discriminant analysis (PCA-LDA). The SERS spectra were acquired using silver nanoparticles synthesized by reduction with hydroxylamine hydrochloride, which were additionally activated with Ca²⁺ 10⁻⁴ M. Results: The addition of Ca(NO₃)₂ 10⁻⁴ M promoted the specific adsorption to the metal surface of the anionic purine metabolites such as uric acid, xanthine and hypoxanthine. Moreover, the SERS spectra of urine were acquired without any filtering or processing step for removing protein traces and other contaminants. Using PCA-LDA, the SERS spectra of urine from breast cancer patients were classified with a sensitivity of 81%, a specificity of 95% and an overall accuracy of 88%. Conclusion: The results of this preliminary study contribute to the translation of SERS in the clinical setting and highlight the potential of SERS as a novel screening strategy for breast cancer.

Background: Worldwide, colorectal cancer (CRC) is the third most common cancer in men and second in women. The aim of the current study was to identify whether the miR-375 is indeed down-regulated in metastatic CRC and if it could be considered as a potential minimally invasive prognostic biomarker for CRC. Methods. Exosomes were isolated and characterized from patients with liver metastasis from CCR. The characterization of exosome was performed using TEM/SEM. HCT116 cells were treated with miR-375 mimic, NSM and miR-375 inhibitor. Functional assays included cell counting assay for 14 days, Matrigel invasion assay, apoptosis assay by flow cytometry using Annexin V-FITC, RT-PCR and Western blotting. Results. Increased proliferation potential was proven for the cells transfected with miR-375 inhibitor, while the miR-375 mimic decreased the cell number. The cells transfected with the miR-375 inhibitor are aggressive and cross the membrane; 3.84% of the cells transfected with the miR-375 inhibitor entered apoptosis, while 6.45% of those transfected with the non-specific mimic were in programmed cell death, less than those transfected with the microRNA. RT-PCR for Bcl-2 expression showed that Bcl-2 is down-regulated for miR-375 inhibitor and up-regulated for the miR-375 mimic, a result confirmed by Western blotting. Conclusion: The present study brings to the forefront new data that suggest miR-375 as a new player in controlling the pathways responsible for inhibiting the natural history of CRC tumor cells, via the Bcl-2 pathway. Abbreviations: APC: adenomatous polyposis coli; CRC: colorectal cancer; EGFR: epidermal growth factor receptor; ERB: Erythroblastic Leukemia Viral Oncogene Homolog; FITC: Fluorescein isothiocyanate; MAPK: mitogen-activated protein-kinase; miR: microRNA; mTOR: mammalian target of rapamycin; NSM: non specific mimic; qRT-PCR: quantitative real time polymerase chain reaction; SEM: scanning electron microscopy; TEM: transmission electron microscopy; TGF-beta: transforming growth factor beta.

The epidermal growth factor receptor (EGFR) plays a critical role in the tumorigenesis of various forms of cancer. Targeting the mutant forms of EGFR has been identified as an attractive therapeutic approach and led to the approval of three generations of inhibitors. The quinazoline core has emerged as a favorable scaffold for the development of novel EGFR inhibitors due to increased affinity for the active site of EGFR kinase. Currently, there are five first-generation (gefitinib, erlotinib, lapatinib, vandetanib, and icotinib) and two second-generation (afatinib and dacomitinib) quinazoline-based EGFR inhibitors approved for the treatment of various types of cancers. The aim of this review is to outline the structural modulations favorable for the inhibitory activity toward both common mutant (del19 and L858R) and resistance-conferring mutant (T790M and C797S) EGFR forms, and provide an overview of the newly synthesized quinazoline derivatives as potentially competitive, covalent or allosteric inhibitors of EGFR.

This study was targeted on a metabolomic approach to compare the blood serum free amino acid profiles and concentration of confirmed breast cancer (stages I–III) patients to healthy controls in order to establish reliable biomarkers of early detection and prediction of breast cancer. The ultra-high-performance liquid chromatography coupled with mass spectrometry using positive ionization electrospray was applied for the picoline-derivatized serum free amino acids using the EZ:faastTM kit. Multivariate statistical analysis principal component analysis, partial least squares discrimination analysis and univariate analysis were applied in order to discriminate between patient groups and putative amino acid biomarkers for breast cancer. A significant decrease of amino acid concentrations between the breast cancer group and the control group was positively correlated with breast cancer progression. Arginine, Alanine, Isoleucine, Tyrosine and Tryptophan were identified as being good potential discriminants (AUROC ≥0.85) and suitable candidates to diagnose and predict the breast cancer progression.

Metabolomics coupled with bioinformatics may identify relevant biomolecules such as putative biomarkers of specific metabolic pathways related to colorectal diagnosis, classification and prognosis. This study performed an integrated metabolomic profiling of blood serum from 25 colorectal cancer (CRC) cases previously classified (Stage I to IV) compared with 16 controls (disease-free, non-CRC patients), using high-performance liquid chromatography and mass spectrometry (UPLC-QTOF-ESI⁺ MS). More than 400 metabolites were separated and identified, then all data were processed by the advanced Metaboanalyst 5.0 online software, using multi- and univariate analysis, including specificity/sensitivity relationships (area under the curve (AUC) values), enrichment and pathway analysis, identifying the specific pathways affected by cancer progression in the different stages. Several sub-classes of lipids including phosphatidylglycerols (phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and PAs), fatty acids and sterol esters as well as ceramides confirmed the “lipogenic phenotype” specific to CRC development, namely the upregulated lipogenesis associated with tumor progression. Both multivariate and univariate bioinformatics confirmed the relevance of some putative lipid biomarkers to be responsible for the altered metabolic pathways in colorectal cancer.