Age-Related Variations in Clinical, Histological, and Genetic Characteristics in Multiple and Familial Melanomas: A Study of 333 Patients.

: Melanoma is an aggressive cutaneous malignancy with a rising incidence. While most cases are sporadic, 5-10% are hereditary, especially in patients with multiple or familial melanomas. The aim of this study is to explore the epidemiological, clinical, histological, and genetic features of this class of patients to identify risk factors for better management and surveillance.

A cell-based Papain-like Protease (PLpro) activity assay for rapid detection of active SARS-CoV-2 infections and antivirals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are a continuous threat to human life. An urgent need remains for simple and fast tests that reliably detect active infections with SARS-CoV-2 and its variants in the early stage of infection. Here we introduce a simple and rapid activity-based diagnostic (ABDx) test that identifies SARS-CoV-2 infections by measuring the activity of a viral enzyme, Papain-Like protease (PLpro).

The Somali Distress and Resilience Scale: Development of a novel measure for Somali adults.

Although resilience has been identified as an important mediator of negative mental health outcomes among refugee populations, there are few culturally specific measures of resilience among such communities and no such measure among Somalis. In this study we aimed to develop a culturally appropriate measure of resilience specific to Somali adults in San Diego, as an example of a vulnerable refugee community. A community-based, exploratory sequential mixed method investigation was conducted via focus group discussions ( = 4), cognitive interviews ( = 4), and iterative survey adaptation.

Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.

Background And Aim: Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.

Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort.

Background: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling.

Methods: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin.

Special Issue "Molecular Advances in Cancer Genetics 3.0".

The third volume of this Special Issue focuses on new advances in cancer genetics studies and collates papers reporting on a variety of mechanisms of tumorigenesis, the need to explore them from multiple perspectives, and the difficulties in exploring them, as well as the challenge of integrating them into a unifying but still different model for each tumor type [...

Germline Variants: A Critical Perspective on Tumor Predisposition Syndrome.

The Protection of Telomere 1 () gene was identified as a melanoma predisposition candidate nearly 10 years ago. Thereafter, various cancers have been proposed as associated with germline variants in the context of the so-called Predisposition Tumor Syndrome (POT1-TPD). While the key role, and related risks, of the alterations in in melanoma are established, the correlation between germline variants and the susceptibility to other cancers partially lacks evidence, due also to the rarity of POT1-TPD.

Pancreatic Cancer: From Genetic Mechanisms to Translational Challenges.

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies in industrialized countries, is predicted to become the second leading cause of cancer deaths by 2040 [...

A Glance at Molecular Advances in Cancer Genetics: A Baffling Puzzle Still to Be Solved.

The purpose of this first Special Issue is to provide a glance at the molecular advances in cancer genetics to untangle the complexity of tumorigenesis [...

The impact of family income and parental factors on children's resilience and mental well-being.

Although there is robust evidence on the intergenerational transmission of trauma-related distress, much less is known about the relation of family income and parental resilience on the resilience and mental well-being of traumatized children. We aimed to determine the association between parental resilience and perceived financial stability, and the resilience and depression of their children among Syrian refugees in Jordan. We carried out a survey of 363 parent-child dyads from a refugee clinic in Northern Jordan.

Ataxia-Telangiectasia Mutated Loss of Heterozygosity in Melanoma.

ATM germline pathogenic variants were recently found enriched in high-risk melanoma patients. However, ATM loss of heterozygosity (LOH) has never been investigated in melanoma and, therefore, a causal association with melanoma development has not been established yet. The purpose of this study was to functionally characterize 13 germline ATM variants found in high-risk melanoma patients-and classified by in silico tools as pathogenic, uncertain significance, or benign-using multiple assays evaluating ATM/pATM expression and/or LOH in melanoma tissues and cell lines.

Predictors of germline status for hereditary melanoma: 5 years of multi-gene panel testing within the Italian Melanoma Intergroup.

Background: The incidence of cutaneous melanoma is increasing in Italy, in parallel with the implementation of gene panels. Therefore, a revision of national genetic assessment criteria for hereditary melanoma may be needed. The aim of this study was to identify predictors of susceptibility variants in the largest prospective cohort of Italian high-risk melanoma cases studied to date.

Beyond BRCA: The Emerging Significance of DNA Damage Response and Personalized Treatment in Pancreatic and Prostate Cancer Patients.

The germline and/or somatic pathogenic variants (PVs) are key players in the hereditary predisposition and therapeutic response for breast, ovarian and, more recently, pancreatic and prostate cancers. Aberrations in other genes involved in homologous recombination and DNA damage response (DDR) pathways are being investigated as promising targets in ongoing clinical trials. However, DDR genes are not routinely tested worldwide.

Insights into Mechanisms of Tumorigenesis in Neuroendocrine Neoplasms.

Genomic studies have identified some of the most relevant genetic players in Neuroendocrine Neoplasm (NEN) tumorigenesis. However, we are still far from being able to draw a model that encompasses their heterogeneity, elucidates the different biological effects consequent to the identified molecular events, or incorporates extensive knowledge of molecular biomarkers and therapeutic targets. Here, we reviewed recent insights in NEN tumorigenesis from selected basic research studies on animal models, highlighting novel players in the intergenic cooperation and peculiar mechanisms including splicing dysregulation, chromatin stability, or cell dedifferentiation.

Germline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortia.

Purpose: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear.

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited.

Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime.

Preferences of Italian patients for return of secondary findings from clinical genome/exome sequencing.

Exome/genome sequencing (ES/GS) is increasingly becoming routine in clinical genetic diagnosis, yet issues regarding how to disclose and manage secondary findings (SFs) remain to be addressed, and limited evidence is available on patients' preferences. We carried out semi-structured interviews with 307 individuals undergoing clinical genetic testing to explore their preferences for return of SFs in the hypothetical scenario that their test would be performed using ES/GS. Participants were 254 females (82.

Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.

Melanoma is one of the most aggressive tumors of the skin, and its incidence is growing worldwide. Historically considered a drug resistant disease, since 2011 the therapeutic landscape of melanoma has radically changed. Indeed, the improved knowledge of the immune system and its interactions with the tumor, and the ever more thorough molecular characterization of the disease, has allowed the development of immunotherapy on the one hand, and molecular target therapies on the other.

The Current State of Molecular Testing in the BRAF-Mutated Melanoma Landscape.

The incidence of melanoma, among the most lethal cancers, is widespread and increasing. Metastatic melanoma has a poor prognosis, representing about 90% of skin cancer mortality. The increased knowledge of tumor biology and the greater understanding of the immune system role in the anti-tumor response has allowed us to develop a more rational approach to systemic therapies.