Hereditary breast and ovarian cancer: from genes to molecular targeted therapies.

Hereditary familial tumors constitute 10-15% of all malignancies and present opportunities for the identification of therapeutic approaches against specific germline genetic defects. Hereditary breast and ovarian cancer (HBOC) syndrome, which is linked to the pathogenic mutations of the breast cancer 1 () and breast cancer 2 () genes, is an important research model for personalized therapeutic approaches for specific germline mutations. HBOC is characterized by multiple cases of breast and ovarian carcinoma in association with other tumors (prostate, pancreas and stomach carcinoma) within the same family branch, a young age of onset (<36 years), bilaterality and an autosomal dominant pattern of inheritance.

Recurrent NF1 gene variants and their genotype/phenotype correlations in patients with Neurofibromatosis type I.

Neurofibromatosis type I, a genetic condition due to pathogenic variants in the NF1 gene, is burdened by a high rate of complications, including neoplasms, which increase morbidity and mortality for the disease. We retrospectively re-evaluated the NF1 gene variants found in the period 2000-2019 and we studied for genotype/phenotype correlations of disease complications and neoplasms 34 variants, which were shared by at least two unrelated families (range 2-11) for a total 141 of probands and 21 relatives affected by Neurofibromatosis type I. Recurrent variants could be ascribed to the most common mutational mechanisms (C to T transition, microsatellite slippage, non-homologous recombination).

COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence.

Background: Homocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID-19 infection. The purpose of this review was to analyze the correlation between the prevalence of MTHFR C677 T gene polymorphism and COVID-19 incidence and mortality worldwide.

Methods: Data regarding MTHFR C677 T gene mutation were obtained from the interrogation of the Genome Aggregation Database (genomAD), which is publicly available from the web"https://gnomad.

Liquid biopsy with cell free DNA: new horizons for prostate cancer.

Although prostate cancer (PCa) is one of the most common tumors in European males, the only minimally invasive diagnostic tool in PCa setup is the determination of PSA in serum. Cell-free DNA (cfDNA) has been demonstrated to be helpful for PCa diagnosis but has not yet been integrated into the clinical setting. This review aims to provide a systematic update of cfDNA and its fragmentation patterns in PCa reported in literature published over the last twenty years.

Biomarkers associated with COVID-19 disease progression.

The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment.

Insights into Genetic Susceptibility to Melanoma by Gene Panel Testing: Potential Pathogenic Variants in ACD, and .

The contribution of recently established or candidate susceptibility genes to melanoma missing heritability has yet to be determined. Multigene panel testing could increase diagnostic yield and better define the role of candidate genes. We characterized 273 and negative probands through a custom-designed targeted gene panel that included and Co-segregation, loss of heterozygosity (LOH)/protein expression analysis, and splicing characterization were performed to improve variant classification.

Clinical, pathological and dermoscopic phenotype of MITF p.E318K carrier cutaneous melanoma patients.

Background: The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined.

Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response.

In difference to other solid malignancies, the identification of biomarkers for the prediction of malignant melanoma (MM) response to immunotherapy is limited. The aim of the current study was to evaluate the immunohistochemical (IHC) expression of MMR proteins in a cohort of MM metastatic patients receiving anti PD-1 treatments. The therapeutic response of patients was also retrospectively assessed.

Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis.

Background: Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis.

Methods: Thirty patients with histologically proven PCa, 33 with benign prostate hyperplasia (BPH) and 21 healthy controls were enrolled.

Non-blood sources of cell-free DNA for cancer molecular profiling in clinical pathology and oncology.

Liquid biopsy can quantify and qualify cell-free (cfDNA) and tumour-derived (ctDNA) DNA fragments in the bloodstream. CfDNA quantification and mutation analysis can be applied to diagnosis, follow-up and therapeutic management as novel oncologic biomarkers. However, some tumor-types release a low amount of DNA into the bloodstream, hampering diagnosis through standard liquid biopsy procedures.

Innovative use of magnesium oxide in the treatment of "neuralgia of the celiac plexus of rheumatic origin" by G. Moscati in 1923.

We presented and discussed one interesting medical prescription by doctor Giuseppe Moscati (1880-1927), who prescribed magnesium oxide (magnesia usta) to a patient with the diagnosis of "neuralgia of the celiac plexus of rheumatic origin". Besides the traditional use of magnesium as antacid remedy at the time, we raised the hypothesis that magnesium could be administered by Moscati in order to treat the neuralgia itself. Considering the scientific background of Moscati at the school of Filippo Bottazzi (1867-1941), a father of Italian biochemistry, we suggested that the doctor tried to apply the preliminary concepts acquired from electrophysiological studies on magnesium to his clinical practice.

Seminal Cell Free DNA Concentration Levels Discriminate Between Prostate Cancer and Benign Prostatic Hyperplasia.

Background/aim: Seminal plasma cfDNA (scfDNA) was recently proposed as a novel PCa biomarker. Our aim was to evaluate whether scfDNA could discriminate PCa from benign prostate hyperplasia (BPH) patients.

Patients And Methods: A cohort of 43 patients (18 and 25 pathology proven PCa and BPH patients), and 13 healthy age-matched control subjects were enrolled.

Dabrafenib-trametinib combination in 'field-practice': an Italian experience.

Aim: This observational study investigates the effectiveness and safety of dabrafenib/trametinib combination in patients with metastatic melanoma.

Patients & Methods: Seventy-six patients treated with dabrafenib/trametinib (150 mg twice daily/2 mg once daily) were included.

Results: Median progression-free survival was 9 months (95% CI: 7-11) and median overall survival was 14 months (11-16); disease control rate was 72%.

Seminal Cell-Free DNA Assessment as a Novel Prostate Cancer Biomarker.

Cell-free DNA (cfDNA) includes circulating DNA fragments, which can be obtained from different human biological samples. cfDNA originates either from apoptotic and/or necrotic cells or is actively secreted by cancer cells. As yet, a quantification and size distribution assessment of seminal plasma cfDNA from prostate cancer patients has never been assessed.

Facts and Misconceptions about 2D:4D, Social and Risk Preferences.

We study how the ratio between the length of the second and fourth digit (2D:4D) correlates with choices in social and risk preferences elicitation tasks by building a large dataset from five experimental projects with more than 800 subjects. Our results confirm the recent literature that downplays the link between 2D:4D and many domains of economic interest, such as social and risk preferences. As for the former, we find that social preferences are significantly lower when 2D:4D is above the median value only for subjects with low cognitive ability.

The value of fluorimetry (Qubit) and spectrophotometry (NanoDrop) in the quantification of cell-free DNA (cfDNA) in malignant melanoma and prostate cancer patients.

Background: Circulating cell-free tumor DNA (cfDNA) is of crucial interest in oncology. cfDNA constitutes a potential prognostic and therapeutic marker for different solid tumors and can be used in the diagnostic and therapeutic management of cancer patients for which nowadays there are no valid laboratory markers. In the present study, the quality and quantity of the cfDNA were assessed by different quantification procedures, in order to identify the potential applications of these techniques in the preliminary cfDNA quantification.

Germline Mutations and the Basaloid Follicular Hamartoma Values in the Tumor Spectrum of Basal Cell Carcinoma Syndrome (NBCCS).

Background/aim: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited disorder characterized by multiple basal cell carcinomas (BCC), odontogenic tumors and various skeletal anomalies. Basaloid follicular hamartomas (BFHs) constitute rare neoplasms that can be detected in sporadic and familial settings as in the Basaloid Follicular Hamartoma Syndrome (BFHS). Although BFHS shares clinical, histopathological and genetic overlapping with the NBCCS, they are still considered two distinctive entities.

, and Advanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival.

Background/aim: The mutational status of stage III and IV melanomas should be recognized in order to allow for targeted therapies. The aim of our study was the characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define their optimal management.

Patients And Methods: Between 1991 and 2015, 63 mutated melanoma patients were treated and monitored during their diagnostic and therapeutic management at a single institution.

Myopic Loss Aversion under Ambiguity and Gender Effects.

Experimental evidence suggests that the frequency with which individuals get feedback information on their investments has an effect on their risk-taking behavior. In particular, when they are given information sufficiently often, they take less risks compared with a situation in which they are informed less frequently. We find that this result still holds when subjects do not know the probabilities of the lotteries they are betting upon.

Desmoplastic melanoma: a challenge for the oncologist.

Aim: To evaluate clinical, pathologic and genetic features of desmoplastic melanoma (DM).

Materials & Methods: Analysis of all DM records from 1991 to 2015.

Results: The most common location of DMs was the head and neck (69%); median age and follow-up were 60.

Giant elephantiasis neuromatosa in the setting of neurofibromatosis type 1: A case report.

Elephantiasis neuromatosa (EN) can arise from a plexiform neurofibroma of the superficial and deep nerves developing from a hyperproliferation of the perineural connective tissue infiltrating adjacent fat and muscles. To date, the clinical association between EN and neurofibromatosis type 1 (NF1) has been poorly defined, particularly with regard to the role of lymphatic alterations and the consequent lymphedema. The present study reports the clinical and biomolecular features of EN in a NF1 patient with the clear clinical diagnostic criteria of multiple cafè-au-lait macules, neurofibromas, EN, a positive family history and a novel NF1 germline c.

Congenital Glioblastoma multiforme and eruptive disseminated Spitz nevi.

Background: Glioblastoma multiforme (GBM) is the deadliest malignant primary brain tumor in adults. GBM develops primarily in the cerebral hemispheres but can develop in other parts of the central nervous system. Its congenital variant is a very rare disease with few cases described in literature.

Fibroepithelioma of Pinkus: Solitary tumor or sign of a complex gastrointestinal syndrome.

Fibroepithelioma of Pinkus (FEP), which is considered to be an uncommon variant of basal cell carcinoma, has been described in association with other systemic diseases. However, no specific studies are currently available on this subject. The aim of our study was to evaluate the clinical and morphological characteristics of FEP and investigate whether this rare tumor is a single entity or seen in the context of a more complex syndrome.