Publications by authors named "Ghiorzo P"

Article Synopsis
  • The effectiveness of a pilot e-learning course on oncogenomics for health professionals was assessed, revealing significant knowledge gains.
  • Nearly 350 Italian professionals, primarily physicians, showed an average post-test score that increased by 19% after completing the course, with older age and southern region residency linked to larger improvements.
  • Participants rated the course highly in terms of methodology, content quality, and usability, indicating strong satisfaction and potential for broader use in professional education.
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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.

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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.

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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 [...

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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.

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Background: The current therapeutic algorithm for Advanced Stage Melanoma comprises of alternating lines of Targeted and Immuno-therapy, mostly via Immune-Checkpoint blockade. While Comprehensive Genomic Profiling of solid tumours has been approved as a companion diagnostic, still no approved predictive biomarkers are available for Melanoma aside from BRAF mutations and the controversial Tumor Mutational Burden. This study presents the results of a Multi-Centre Observational Clinical Trial of Comprehensive Genomic Profiling on Target and Immuno-therapy treated advanced Melanoma.

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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 [...

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Background: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark-skinned individuals, are underrepresented.

Objectives: We report a comprehensive pooled analysis of established high- and intermediate-penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium.

Methods: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed.

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Pancreatic adenocarcinoma is a highly aggressive disease with a poor prognosis. The reprogramming of energetic metabolism has long been implicated in pancreatic tumorigenesis and/or resistance to treatment. Considering that long non-coding RNA dysregulation has been described both in cancerogenesis and in the altered homeostasis of several metabolic pathways, metabolism-associated lncRNAs can contribute to pancreatic cancer evolution.

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Article Synopsis
  • The study investigates how whole-exome sequencing and circulating free DNA (cfDNA) can help predict therapy response in metastatic melanoma patients during treatment.
  • Non-responders showed more genetic variations and mutations in key melanoma genes compared to responders, especially in those with the V600 mutation.
  • The study also found that factors like tumor mutational burden (TMB), loss of heterozygosity (LOH), and tumor ploidy were linked to therapy resistance, suggesting that genomic testing can provide insights into treatment outcomes.
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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 [...

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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.

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Article Synopsis
  • The study investigates the role of specific genes in pancreatic ductal adenocarcinoma (PDAC), particularly focusing on patients with germline pathogenic variants (GPVs) and those without.
  • Researchers analyzed data from 189 cancer predisposition genes through various statistical tests to find potential associations with PDAC in different patient groups.
  • Results indicate that certain genes show strong links to PDAC in GPV patients, while others emerge as new candidates for non-GPV patients, suggesting distinct genetic factors underlying PDAC in these populations.
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Article Synopsis
  • Multigene germline panel testing is advised for pancreatic cancer patients, but the effectiveness beyond BRCA1/2 is uncertain.
  • A study of 422 Italian pancreatic cancer patients revealed that 17% had pathogenic variants, primarily in BRCA1/2 and CDKN2A, and those with these variants tended to be younger and have a family history of related cancers.
  • Patients with pathogenic variants experienced improved overall survival rates, suggesting that genes like CDKN2A and ATM should be included in genetic testing, regardless of family history.
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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.

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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.

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The development of innovative technologies and the advances in the genetics and genomics, have offered new opportunities for personalized treatment in oncology. Although the selection of the patient based on the molecular characteristics of the neoplasm has the potential to revolutionize the therapeutic scenario of oncology, this approach is extremely challenging. The access, homogeneity, and economic sustainability of the required genomic tests should be warranted in the clinical practice, as well as the specific scientific and clinical expertise for the choice of medical therapies.

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Background: A polygenic inheritance involving high, medium and low penetrance genes has been suggested for melanoma susceptibility in adults, but genetic information is scarce for paediatric patients.

Objective: We aim to analyse the major high and intermediate melanoma risk genes, CDKN2A, CDK4, POT1, MITF and MC1R, in a large multicentre cohort of Italian children and adolescents in order to explore the genetic context of paediatric melanoma and to reveal potential differences in heritability between children and adolescents.

Methods: One-hundred-twenty-three patients (<21 years) from nine Italian centres were analysed for the CDKN2A, CDK4, POT1, MITF, and MC1R melanoma predisposing genes.

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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.

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The 10q24.33 locus is known to be associated with susceptibility to cutaneous malignant melanoma (CMM), but the mechanisms underlying this association have been not extensively investigated. We carried out an integrative genomic analysis of 10q24.

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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.

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While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novel NRAS variant (c.170A > C, p.

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Article Synopsis
  • The first International Workshop on the ATM gene and cancer took place on December 4-5, 2019, in Paris, focusing on the gene's role in various cancers due to the presence of germline ATM pathogenic variants.
  • Experts from different fields discussed the lack of consensus on management guidelines for these variant carriers because of insufficient age-, sex-, and site-specific risk estimates.
  • The meeting emphasized the need for large-scale studies to enhance cancer risk management and therapeutic strategies for ATM variant carriers beyond Ataxia-Telangiectasia.
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