Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome.

Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs.

Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background.

Using multigene panel testing for the diagnostic evaluation of patients with hereditary breast and ovarian cancer (HBOC) syndrome often identifies clinically actionable variants in genes with varying levels of penetrance. High-penetrance genes (, , , , , , ) inform specific clinical surveillance and therapeutic decisions, while recommendations for moderate-penetrance genes (, , , , , , , , , , , ) are more limited. A detailed disease history, including pedigree data, helps formulate the most appropriate and personalised management strategies.

Genetic landscape of Romanian PPGLs.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that originate from chromaffin cells and occur in the adrenal medulla and in the sympathetic or parasympathetic ganglia. Nearly 70% of PPGLs result from germline or somatic mutations in a single driver gene. The aim of this study was to characterize the genetic background and clinical characteristics related to genetic profile of patients with PPGLs from Romania.

Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies.

Glucocorticoid receptor (GR) activation may promote metastasis in oestrogen receptor-negative and triple-negative breast cancer (TNBC). However, the role of the GRβ isoform, which has opposing effects to the main isoform, has not been studied in clinical samples. We aimed to analyse the intracellular localisation of total GR and GRβ in vitro using plasmid constructs and fluorescent immunocytochemistry.

Prediction of PSA Response after Dexamethasone Switch during Abiraterone Acetate + Prednisolone Treatment of Metastatic Castration-Resistant Prostate Cancer Patients.

Background: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods: If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients' history was used to find the best model in a cohort of 67 patients.

[Examination of breast density in breast cancer discordant twin pairs].

Previous twin studies show that genetic factors are responsible for 63% of the variability in breast density. We analyzed the mammographic images of 9 discordant twin pairs for breast cancer from the population-based Hungarian Twin Registry. We measured breast density using 3D Slicer software.

Circulating non-coding RNA biomarkers of endocrine tumours.

Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background.

Application of comprehensive molecular genetic profiling in precision cancer medicine, Hungarian experiences.

Unlabelled: Recent developments in molecular genetic testing methods (e.g. next-generation sequencing [NGS]-panels) largely accelerated the process of finding the most appropriate targeted therapeutic intervention for cancer patients based on molecularly targetable genetic alterations.

Cost-effectiveness of Genetic Testing of Endocrine Tumor Patients Using a Comprehensive Hereditary Cancer Gene Panel.

Introduction: Heterogenous clinical manifestations, overlapping phenotypes, and complex genetic backgrounds are common in patients with endocrine tumors. There are no comprehensive recommendations for genetic testing and counseling of these patients compared to other hereditary cancer syndromes. The application of multigene panel testing is common in clinical genetic laboratories, but their performance for patients with endocrine tumors has not been assessed.

Bilateral pheochromocytomas: clinical presentation and morbidity rate related to surgery technique and genetic status.

Background: Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60-90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients.

[The epidemiology of primary brain malignancies].

The occurrence of central nervous system malignancies is relatively low; however, these tumors exhibit poor prognosis and a high mortality rate. On epidemiological grounds, Hungary was placed in the last third among European countries: in the last decade annually 750 to 1000 new cases were diagnosed and the number of deaths was between 550 and 690, without any apparent trends. Age distribution analyses revealed childhood peak and a higher peak at around 65 years of age.

Double Heterozygosity for Rare Deleterious Variants in the and Genes in a Hungarian Patient with Breast Cancer.

Hereditary breast cancer is most commonly attributed to germline and gene variants. The vast majority of and mutation carriers are single heterozygotes, and double heterozygosity (DH) is a very rare finding. Here, we describe the case of a / double heterozygous female proband diagnosed with breast cancer.

A new method to quantify the effect of co-medication on the efficacy of abiraterone in metastatic castration-resistant prostate cancer patients.

Patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) have co-morbidities treated with different drugs. The aim was to quantify the potential effect of co-medications on AA treatment duration (TD) and overall survival (OS). A new parameter, called "individual drug score" (IDS) was calculated by summing the "drug score"-s (DS) of all co-medications for each patient.

Variants Extend the Mutational Profile of Hungarian Patients with Breast and Ovarian Cancer.

Background: The pathogenic/likely pathogenic (P/LP) variant detection rate and profile of , the third most important breast cancer gene, may vary between different populations.

Methods: was analyzed in peripheral blood samples of three independent cohorts: prospectively between September 2021 and March 2023 (i) in 1280 consecutive patients with breast and/or ovarian cancer (HBOC), (ii) in 568 patients with other cancers (controls), and retrospectively, (iii) in 191 young breast cancer (<33 years, yBC) patients. These data were compared with data of 134,187 non-cancer individuals retrieved from the Genome Aggregation Database.

Whole genome sequencing resolves 10 years diagnostic odyssey in familiar myxoma.

Carney complex (CNC) is an ultrarare disorder causing cutaneous and cardiac myxomas, primary pigmented nodular adrenocortical disease, hypophyseal adenoma, and gonadal tumours. Genetic alterations are often missed under routine genetic testing. Pathogenic variants in PRKAR1A are identified in most cases, while large exonic or chromosomal deletions have only been reported in a few cases.

Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre.

TP53 variant interpretation is still challenging, especially in patients with attenuated Li-Fraumeni syndrome (LFS). We investigated the prevalence of pathogenic/likely pathogenic (P/LP) variants and LFS disease in the Hungarian population of cancer patients. By testing 893 patients with multiplex or familial cancer, we identified and functionally characterized novel splice variants of TP53 helping accurate variant classification.

[Macronodular adrenal hyperplasia causing Cushing's syndrome due to ARMC5 gene mutation.].

Our 69-year-old female patient was investigated for a 20 kg weight gain over 2 years. The patient's medical history included hypertension, hyperuricemia, bilateral cataract surgery and musculosceletal complaints. Diabetes mellitus was not found.

Context-Dependent Role of Glucocorticoid Receptor Alpha and Beta in Breast Cancer Cell Behaviour.

. The dual role of GCs has been observed in breast cancer; however, due to many concomitant factors, GR action in cancer biology is still ambiguous. In this study, we aimed to unravel the context-dependent action of GR in breast cancer.

A common genetic variation in may associate with cancer risk in patients with Lynch syndrome.

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is a common genetic predisposition to cancer due to germline mutations in genes affecting DNA mismatch repair. Due to mismatch repair deficiency, developing tumors are characterized by microsatellite instability (MSI-H), high frequency of expressed neoantigens and good clinical response to immune checkpoint inhibitors. Granzyme B (GrB) is the most abundant serine protease in the granules of cytotoxic T-cells and natural killer cells, mediating anti-tumor immunity.

Genome sequencing-based discovery of a novel deep intronic APC pathogenic variant causing exonization.

Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome that occurs as a result of germline mutations in the APC gene. Despite a clear clinical diagnosis of FAP, a certain proportion of the APC variants are not readily detectable through conventional genotyping routines. We accomplished genome sequencing in duo of the disease-affected proband and non-affected sibling followed by in silico predictions and a series of RNA-based assays clarifying variant functionality.

Quantitative PCR from human genomic DNA: The determination of gene copy numbers for congenital adrenal hyperplasia and RCCX copy number variation.

Quantitative PCR (qPCR) is used for the determination of gene copy number (GCN). GCNs contribute to human disorders, and characterize copy number variation (CNV). The single laboratory method validations of duplex qPCR assays with hydrolysis probes on CYP21A1P and CYP21A2 genes, residing a CNV (RCCX CNV) and related to congenital adrenal hyperplasia, were performed using 46 human genomic DNA samples.