Defactinib in Combination with Mitotane Can Be an Effective Treatment in Human Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is an aggressive cancer with a poor prognosis. Mitotane, the only FDA-approved treatment for ACC, targets adrenocortical cells and reduces cortisol levels. Although it remains the cornerstone of systemic therapy, its overall impact on long-term outcomes is still a matter of ongoing clinical debate.

Challenges in circulating miRNA analysis in adrenocortical tumors.

The differentiation of benign and malignant adrenocortical tumors is of major clinical relevance. Circulating microRNAs (miRNAs) hold promise as blood-borne biomarkers of adrenocortical cancer (ACC). There are, however, many difficulties with their use, including technical and biological standardization challenges.

[Germline mutations define the prognosis and therapy of pheochromocytomas and paragangliomas].

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, where the genetic background is of particular importance in terms of the diagnosis, follow-up, treatment and prognosis of the disease. Although the prognosis in benign cases is encouraging, in the case of malignant disease the mortality rates are dramatically worse due to the high tumor burden and possible cardiovascular complications caused by catecholamine oversecretion. In recent years, significant progress has been made both in the functional imaging of the disease and in the therapy of malignant diseases, which in many cases are also related to the underlying genetic background.

[Pathogenic large duplication in TP53 as a hereditary predisposing factor in breast cancer].

Aim: Germline pathogenic variants of TP53 are associated with Li-Fraumeni syndrome and represent a high risk for hereditary breast and ovarian cancer. We identified a germline, multi-exon heterozygous duplication variant in TP53, NM_000546.6:dup(ex2-5), in a young triple-negative breast cancer patient.

[Pathogenic role of CHEK2 variants in Hungarian cancer patients: implications for breast cancer risk and genetic counselling].

Aim: Our study assessed the prevalence of CHEK2 gene variants, including low-penetrance variants (lp-CHEK2: p.I157T, p.S428F, p.

[First results of comprehensive genomic studies on solid tumours in National Institute of Oncology].

Aims: The Molecular Pathology Laboratory of the National Institute of Oncology has been performing comprehensive genomic studies (500-gene panel) since 2021. This paper summarizes our results obtained between 2022 and 2024, focusing on clinical requests, the histological type of cases studied and the potential therapeutic benefit of identified variants.

Methods: Comprehensive genomic profiling was performed using next generation sequencing on an Ion S5 Plus system (Thermo Fisher Scientific) with Oncomine Comprehensive Assay Plus kit.

[The status of precision medicine in Hungary in the light of European practice].

Background And Aim: Molecular genetic diagnostics is a complex process, most modern laboratory technologies, IT procedures, data management, medical decision support systems, databases and algorithms are used together. Oncological treatments are expensive procedures and the effectiveness of individual therapies varies in different subtypes of cancer. Nowadays, agnostic approach is increasingly emerging in oncological treatments, i.

The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics.

The glucocorticoid receptor (GR) plays a significant role in breast cancer cell behaviour, although data on its effects are conflicting. The impact of GR agonist dexamethasone (dex) and antagonist mifepristone (mif) on oestrogen-positive (ER+) and triple-negative (TN) breast cancer cell lines in both 2D and 3D cultures was studied using multiple in vitro functional assays and transcriptome sequencing. GR activation increased cell motility in TN but not in ER + tumour cells, as observed in both collective and single-cell migration tests.

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.