Developments in Genetics: Better Management of Ovarian Cancer Patients.

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing and to properly classify all ovarian cancers. In this article, we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels, details about the genes, and also candidate genes. We hope to bring new information to the medical field so as to better prevent and diagnose ovarian cancer.

Homologous Recombination Deficiency Score Determined by Genomic Instability in a Romanian Cohort.

The Homologous Recombination Deficiency (HRD) Score, determined by evaluating genomic instability through the assessment of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST), serves as a crucial biomarker for identifying patients who might benefit from targeted therapies, such as PARP inhibitors (PARPi). This study aimed to investigate the efficacy of HRD testing in high-grade serous ovarian carcinoma, tubal, and peritoneal cancer patients who are negative for somatic BRCA1 and BRCA2 mutations and to evaluate the impact of HRD status on Bevacizumab and PARPi therapy response. A cohort of 100 Romanian female patients, aged 42-77, was initially selected. Among them, 30 patients had unsuitable samples for HRD testing due to insufficient tumor content or DNA integrity. Using the OncoScan C.N.V. platform, HRD testing was successfully performed on the remaining 70 patients, with 20 testing negative and 50 testing positive for HRD. Among the HRD-positive patients, 35 were eligible for and benefited from PARPi maintenance therapy, resulting in a median progression-free survival (PFS) increase from 4 months to 8.2 months. Our findings support the importance of HRD testing in ovarian cancer patients, demonstrating the potential therapeutic advantage of PARPi therapy in HRD-positive patients without somatic BRCA1/2 mutations.

PAH Pathogenic Variants and Clinical Correlations in a Group of Hyperphenylalaninemia Patients from North-Western Romania.

Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene and is characterized by altered amino acid metabolism. More than 1500 known PAH variants intricately determine a spectrum of metabolic phenotypes. We aim to report on clinical presentation and PAH variants identified in 23 hyperphenylalaninemia (HPA)/PKU Romanian patients. Our cohort exhibited classic PKU (73.9%, 17/23), mild PKU (17.4%, 4/23), and mild HPA (8.7%, 2/23). Severe central nervous system sequelae are frequent in our cohort in late-diagnosis symptomatic patients, which highlights yet again the significance of an early dietary treatment, neonatal screening and diagnosis, and facilitated access to treatment. Next-generation sequencing (NGS) identified a total of 11 PAH pathogenic variants, all previously reported, mostly missense changes (7/11) in important catalytic domains. c.1222C>T p.Arg408Trp was the most frequent variant, with an allele frequency of 56.5%. Twelve distinct genotypes were identified, the most frequent of which was p.Arg408Trp/p.Arg408Trp (34.8%, 8/23). Compound heterozygous genotypes were common (13/23), three of which had not been previously reported to the best of our knowledge; two correlated with cPKU and one showed an mPKU phenotype. Generally, there are genotype-phenotype correlation overlaps with the public data reported in BIOPKUdb; as our study shows, clinical correlates are subject to variation, in part due to uncontrolled or unknown epigenetic or environmental regulatory factors. We highlight the importance of establishing the genotype on top of using blood phenylalanine levels.