De novo germline pathogenic variant in Lynch Syndrome: A rare event or the tip of the iceberg?

Lynch Syndrome is an autosomal dominant cancer predisposition syndrome caused by germline pathogenic variants or epimutation in one of the DNA mismatch repair genes. De novo pathogenic variants in mismatch repair genes have been described as a rare event in Lynch Syndrome (1-5%), although the prevalence of de novo pathogenic variants in Lynch Syndrome is probably underestimated. The de novo pathogenic variant was identified in a 26-year-old woman diagnosed with an adenocarcinoma of the caecum with mismatch repair protein deficiency at immunohistochemistry and a synchronous neuroendocrine tumor of the appendix with normal expression of mismatch repair proteins.

OncoPan: An NGS-Based Screening Methodology to Identify Molecular Markers for Therapy and Risk Assessment in Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer has a high morbidity and mortality with the majority being PC ductal adenocarcinomas (PDAC). Whole genome sequencing provides a wide description of genomic events involved in pancreatic carcinogenesis and identifies putative biomarkers for new therapeutic approaches. However, currently, there are no approved treatments targeting driver mutations in PDAC that could produce clinical benefit for PDAC patients.

[HLA-B58.01 and allopurinol hypersensitivity renal vasculitis in a Chinese patient].

Introduction: Allopurinol, widely used in the treatment of hyperuricemia and gout, has been shown to cause severe cutaneous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as systemic reactions such as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). The HLA-B*5801 allele is known to be a risk factor for severe cutaneous manifestations of hypersensitivity to allopurinol, mostly in Asian populations.

Observation: We report the observation of a 47-year-old Chinese patient, with no previous medical history, carrying the HLA-B*5801 allele, who developed an isolated allopurinol hypersensitivity necrotizing renal vasculitis without cutaneous manifestations.

Quantitative MRI analysis of structural changes in tomato tissues resulting from dehydration.

A quantitative magnetic resonance imaging (MRI) analysis at 1.5T of the effects of different dehydration regimes on transverse relaxation parameters measured in tomato tissue is presented. Multi-exponential T maps have been estimated for the first time, providing access to spatialized microstructural information at voxel scale.

A global non-invasive methodology for the phenotyping of potato under water deficit conditions using imaging, physiological and molecular tools.

Background: Drought is a major consequence of global heating that has negative impacts on agriculture. Potato is a drought-sensitive crop; tuber growth and dry matter content may both be impacted. Moreover, water deficit can induce physiological disorders such as glassy tubers and internal rust spots.

Impact of chemical exchange on transverse relaxation at low and moderate magnetic field strengths for sugar solutions representative of fruit tissues analyzed by simulation and MRI experiments.

Proton exchange effects on transverse relaxation rate were studied at low and moderate magnetic fields. Analysis was conducted on low-concentrate simple sugar (fructose and glucose) solutions modeling the vacuolar liquid in fruits. Simulated data obtained from Carver and Richards equations were used to analyze the effects of temperature and pH on parameters involved in the chemical exchange mechanisms.

Campylobacter jejuni infection associated with miscarriage, a case report and literature review.

Campylobacter jejuni is recognized as a cause of miscarriage in animals, but rarely in humans. We describe here a case of spontaneous miscarriage at 12 weeks of gestation associated with Campylobacter jejuni bacteremia following digestive disorders. The patient was treated with azithromycin with good clinical evolution and underwent uterine aspiration during hospitalization.

Development, technical validation, and clinical application of a multigene panel for hereditary gastrointestinal cancer and polyposis.

Introduction: Recent advances in technology and research are rapidly changing the diagnostic approach to hereditary gastrointestinal cancer (HGIC) syndromes. Although the practice of clinical genetics is currently transitioning from targeted criteria-based testing to multigene panels, important challenges remain to be addressed. The aim of this study was to develop and technically validate the performance of a multigene panel for HGIC.

NMR study of fresh cut salads: Influence of temperature and storage time on leaf structure and water distribution in escarole.

Consumption of fresh-cut vegetables has rapidly increased over the past decades. Among salads, escarole is one of the most popular varieties. Specific packaging limits gas exchange and consequently water loss and bacterial respiration, increasing the shelf life of salads.

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.

Objective: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370.

MRI investigation of subcellular water compartmentalization and gas distribution in apples.

Water status and distribution at subcellular level in whole apple fruit were evaluated by Magnetic Resonance Imaging (MRI) measurement of the multi-exponential transverse (T2) relaxation of water protons. Apparent microporosity, also estimated by MRI, provided mapping of gas distribution in fruit tissues. Measuring for the first time the multi-exponential relaxation of water and apparent tissue microporosity in whole fruit and combining these with histological measurements provided a more reliable interpretation of the origins of variations in the transverse relaxation time (T2) and better characterization of the fruit tissue.

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.

Assessment of nutrient remobilization through structural changes of palisade and spongy parenchyma in oilseed rape leaves during senescence.

Differential palisade and spongy parenchyma structural changes in oilseed rape leaf were demonstrated. These dismantling processes were linked to early senescence events and associated to remobilization processes. During leaf senescence, an ordered cell dismantling process allows efficient nutrient remobilization.

Translational and rotational diffusion of flexible PEG and rigid dendrimer probes in sodium caseinate dispersions and acid gels.

The dynamics of rigid dendrimer and flexible PEG probes in sodium caseinate dispersions and acid gels, including both translational diffusion and rotational diffusion, were studied by NMR. Above the onset of the close-packing limit (C ∼ 10 g/100 g H2 O), translational diffusion of the probe depended on its flexibility and on the fluctuations of the matrix chains. The PEG probe diffused more rapidly than the spherical dendrimer probe of corresponding hydrodynamic radius.

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2).

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk.

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.

Structural changes in senescing oilseed rape leaves at tissue and subcellular levels monitored by nuclear magnetic resonance relaxometry through water status.

Nitrogen use efficiency is relatively low in oilseed rape (Brassica napus) due to weak nitrogen remobilization during leaf senescence. Monitoring the kinetics of water distribution associated with the reorganization of cell structures, therefore, would be valuable to improve the characterization of nutrient recycling in leaf tissues and the associated senescence processes. In this study, nuclear magnetic resonance (NMR) relaxometry was used to describe water distribution and status at the cellular level in different leaf ranks of well-watered plants.

Probe mobility in native phosphocaseinate suspensions and in a concentrated rennet gel: effects of probe flexibility and size.

Pulsed field gradient nuclear magnetic resonance and proton nuclear magnetic resonance relaxometry were used to study the self-diffusion coefficients and molecular dynamics of linear (PEGs) and spherical probes (dendrimers) in native phosphocaseinate suspensions and in a concentrated rennet gel. It was shown that both the size and the shape of the diffusing molecules and the matrix topography affected the diffusion and relaxation rates. In suspensions, both translational and rotational diffusion decreased with increasing casein concentrations due to increased restriction in the freedom of motion.

MSE-MRI sequence optimisation for measurement of bi- and tri-exponential T2 relaxation in a phantom and fruit.

The transverse relaxation signal from vegetal cells can be described by multi-exponential behaviour, reflecting different water compartments. This multi-exponential relaxation is rarely measured by conventional MRI imaging protocols; mono-exponential relaxation times are measured instead, thus limiting information about of the microstructure and water status in vegetal cells. In this study, an optimised multiple spin echo (MSE) MRI sequence was evaluated for assessment of multi-exponential transverse relaxation in fruit tissues.

Molecular mobility in dense protein systems: an investigation through 1H NMR relaxometry and diffusometry.

Understanding how proteins behave in highly concentrated systems is a major issue in many fields of research, including biology, biophysics, and chemical engineering. In this paper, we provide a comprehensive (1)H NMR study of molecular mobility in dilute to highly concentrated dispersions of the exact same protein (casein) but organized in two distinct supramolecular forms: spongelike casein micelles or soft casein aggregates. Both relaxometry and diffusometry experiments were performed, so that three different parameters are reported: spin-spin relaxation rates of non-water protons (1/T(2,ne)), spin-spin relaxation rates of water protons (1/T(2,e+w)), and water self-diffusion coefficients (D(w)).

Sequencing analysis of SLX4/FANCP gene in Italian familial breast cancer cases.

Breast cancer can be caused by germline mutations in several genes that are responsible for different hereditary cancer syndromes. Some of the genes causing the Fanconi anemia (FA) syndrome, such as BRCA2, BRIP1, PALB2, and RAD51C, are associated with high or moderate risk of developing breast cancer. Very recently, SLX4 has been established as a new FA gene raising the question of its implication in breast cancer risk.