Genomics in Lung Cancer: A Scoping Review of the Role of ctDNA in Non-Advanced Non-Small-Cell Lung Cancer in the Prediction of Prognosis After Multimodality Therapeutic Approaches.

: Circulating tumor DNA (ctDNA), shed into bodily fluids by cancer cells through apoptosis, necrosis, or active secretion, is currently used in the field of genomic investigation in clinical settings, primarily for advanced stages of non-small-cell lung cancer (NSCLC). However, its potential role in guiding the multi-omic approach to early-stage NSCLC is emerging as a promising area of investigation. Efforts are being made to integrate the genomics not only in surgery, but also in the definition of long-term prognosis after surgical or radiotherapy and for the prediction of recurrence.

Pilomatricoma in Syndromic Contexts: A Literature Review and a Report of a Case in Apert Syndrome.

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein-Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome.

Comprehensive genomic profiling and clinico-pathologic characterization of primary ovarian leiomyosarcoma.

Objective: Primary ovarian leiomyosarcomas are exceptionally rare, accounting for less than 0.1% of ovarian malignancies. Their treatment strategies remain poorly defined, and data on comprehensive genomic profiling are lacking.

Enhanced response to dabrafenib plus trametinib in a patient with lung cancer harboring an variant of unknown significance: a case report.

Background: Literature evidence reports that (ring finger protein 43) gene mutations could serve as predictive biomarkers of response to certain anti-cancer therapies. To delve deeper into the specific role of mutations in lung cancer and their relevance to therapy response, we provide the first report of marked efficacy of the dabrafenib and trametinib therapeutic combination in a patient with microsatellite-stable (MSS) non-small-cell lung cancer (NSCLC) with and mutations.

Case Description: An 85-year-old patient was diagnosed with NSCLC with the presence of MSS, and mutations.

Screening and Identification of a Common Haplotype in the Jewish Community of Rome Reveal a Founder Effect for the c.7007G>C, p. (Arg2336Pro) Variant.

Background/objectives: Cancer risk-reducing strategies in Ashkenazi women carrying founder variants have a cost-effective effect on reducing cancer morbidity and mortality. The British and US guidelines recommend () screening among Ashkenazi Jewish people to identify high-risk individuals. status has not been investigated yet in the Jewish community of Rome.

A Case Report to Reflect on the Origins of MMRd Mesonephric-like Ovarian Adenocarcinoma: Can It Be Defined as a Mϋllerian Neoplasm?

Mesonephric-like adenocarcinoma (MLA) of ovaries is a new and rare neoplastic entity, recently classified by the World Health Organization. Its morphological and immunohistochemical profile is similar to primitive cervical mesonephric adenocarcinoma, but its origin has not been determined yet. Some authors believe that this neoplasm originates from Wolffian remnants in the ovarian hilum, while others suggest an origin from the Mϋllerian epithelium, followed by a mesonephric trans-differentiation.

The Role of ctDNA for Diagnosis and Histological Prediction in Early Stage Non-Small-Cell Lung Cancer: A Narrative Review.

Circulating tumor DNA (ctDNA) may be released from neoplastic cells into biological fluids through apoptosis, necrosis, or active release. In patients with non-small-cell lung cancer (NSCLC), ctDNA analysis is being introduced in clinical practice only for advanced disease management. Nevertheless, an interesting and promising field of application is the analysis of ctDNA in the management of early stage non-small-cell lung cancer, both for evaluation before treatment, such as diagnosis and screening, and for prediction of histology or pathological features.

Beyond the BRCA1/2 genes in ovarian cancer: the role of germline pathogenic variants in the ATM gene.

Background: Ovarian Cancer (OC) prevention and early-stage detection represents a challenge due to the lack of effective surveillance. The identification of high-risk women is crucial as it provides access to prophylactic oophorectomy and reduces disease burden. Next-Generation Sequencing approaches enable the investigation of several genes associated with monogenic hereditary cancer predisposition, including ovarian cancer.

Mesonephric-like adenocarcinoma of the endometrium: detailed molecular characterization of the first case showing a morphological continuum from mesonephric-like metaplasia and atypical mesonephric-like hyperplasia to adenocarcinoma.

Mesonephric-like adenocarcinoma is a rare subtype of endometrial cancer, characterized by its histological and molecular overlap with mesonephric carcinoma of the uterine cervix. This study presents a unique case of mesonephric-like adenocarcinoma in the endometrium, accompanied by adjacent mesonephric-like hyperplasia and atypical mesonephric-like hyperplasia. Histologically, the transition from mesonephric metaplasia to adenocarcinoma was evident, and molecular analysis revealed shared mutations, including KRAS (p.

POLE mutations in endometrial carcinoma: Clinical and genomic landscape from a large prospective single-center cohort.

Background: To date, 11 DNA polymerase epsilon (POLE) pathogenic variants have been declared "hotspot" mutations. Patients with endometrial cancer (EC) characterized by POLE hotspot mutations (POLEmut) have exceptional survival outcomes. Whereas international guidelines encourage deescalation of adjuvant treatment in early-stage POLEmut EC, data regarding safety in POLEmut patients with unfavorable characteristics are still under investigation.

Characterization of shared neoantigens landscape in Mismatch Repair Deficient Endometrial Cancer.

Endometrial cancer (EC) with Mismatch Repair deficiency (MMRd) is characterized by the accumulation of insertions/deletions at microsatellite sites. These mutations lead to the synthesis of frameshift peptides (FSPs) that represent tumor-specific neoantigens (nAg) proved to be shared across patients/tumors with MMRd. In this study, we explored the feasibility of a nAg-based cancer vaccination design in EC with MMRd.

Germline reflex BRCA1/2 testing following tumor-only comprehensive genomic profiling: why, when, and how.

The majority of tumor comprehensive genomic profiling (CGP) currently does not include a matched normal control. The use of a tumor-only CGP approach needs the development of a strategy to refine germline pathogenic/likely pathogenic variants (gP/LPVs) calls, so as to limit the performance of unnecessary germline reflex tests and instead successfully identify patients who are carriers of likely gP/LPVs. Guidelines have been developed for the identification of gP/LPVs in BRCA1/2 genes on the basis of tumor-only CGP results and for the evaluation of the appropriateness of performing germline reflex BRCA1/2 testing.

Pathogenic G6PD variants: Different clinical pictures arise from different missense mutations in the same codon.

G6PD deficiency results from mutations in the X-linked G6PD gene. More than 200 variants are associated with enzyme deficiency: each one of them may either cause predisposition to haemolytic anaemia triggered by exogenous agents (class B variants), or may cause a chronic haemolytic disorder (class A variants). Genotype-phenotype correlations are subtle.

MOREOVER: multiomics MR-guided radiotherapy optimization in locally advanced rectal cancer.

Background: Complete response prediction in locally advanced rectal cancer (LARC) patients is generally focused on the radiomics analysis of staging MRI. Until now, omics information extracted from gut microbiota and circulating tumor DNA (ctDNA) have not been integrated in composite biomarkers-based models, thereby omitting valuable information from the decision-making process. In this study, we aim to integrate radiomics with gut microbiota and ctDNA-based genomics tracking during neoadjuvant chemoradiotherapy (nCRT).

An integrated multitool analysis contributes elements to interpreting unclassified factor IX missense variants associated with hemophilia B.

Background: Dissection of genotype-phenotype relationships in hemophilia B (HB) is particularly relevant for challenging (mild HB) or for HB-associated but unclassified factor (F)IX missense variants.

Objective: To contribute elements to interpret unclassified HB-associated FIX missense variants by a multiple-level approach upon identification of a reported, but uncharacterized, FIX missense variant associated with mild HB.

Methods: Molecular modeling of wild-type and V92A FIX variants, expression studies in HEK293 cells with evaluation of protein (ELISA, western blotting) and activity (activated partial thromboplastin time-based/chromogenic assays) levels after recombinant expression, and multiple prediction tools.