The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population.

Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited.

Relation between HLA and copy number variation of steroid 21-hydroxylase in a Swedish cohort of patients with autoimmune Addison's disease.

Objective: Autoantibodies against the adrenal enzyme 21-hydroxylase is a hallmark manifestation in autoimmune Addison's disease (AAD). Steroid 21-hydroxylase is encoded by CYP21A2, which is located in the human leucocyte antigen (HLA) region together with the highly similar pseudogene CYP21A1P. A high level of copy number variation is seen for the 2 genes, and therefore, we asked whether genetic variation of the CYP21 genes is associated with AAD.

Domain landscapes of somatic NF1 mutations in pheochromocytoma and paraganglioma.

Pheochromocytoma and paraganglioma (PPGL), are rare neuroendocrine tumors arising from the adrenal medulla and extra-adrenal paraganglia, respectively. Up to about 60% are explained by germline or somatic mutations in one of the major known susceptibility genes e.g.

Case report: Two sisters with a germline variant and distinct endocrine neoplasias.

Genetic testing has become the standard of care for many disease states. As a result, physicians treating patients who have tumors often rely on germline genetic testing results for making clinical decisions. Cases of two sisters carrying a germline variant are highlighted whereby possible other genetic drivers were discovered on tumor analysis (also referred to as CHK2) loss of function has been firmly associated with breast cancer development.

Nuclear and mitochondrial DNA alterations in pheochromocytomas and paragangliomas, and their potential treatment.

Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is little information about its involvement in pheochromocytomas and paragangliomas (PCCs/PGLs) formation. PCCs and PGLs are rare endocrine tumors of the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia that can synthesize and secrete catecholamines.

Methylation associated with long- or short-term survival in glioblastoma patients from the Nordic phase 3 trial.

Patients with glioblastoma (GBM) have a poor outcome, but even among patients receiving the same therapies and with good prognostic factors, one can find those with exceptionally short and long survival. From the Nordic trial, which randomized GBM patients of 60 years or older between two radiotherapy arms (60 Gy or 34 Gy) or temozolomide (TMZ), we selected 59 with good prognostic factors. These selected GBM patients were equally distributed according to treatment and MGMT promoter methylation status but had long or short survival.

Glucocerebrosidase variant T369M is not a risk factor for Parkinson's disease in Sweden.

Introduction: Genetic variants in the Beta-glucocerebrosidase gene (GBA1) is a known risk factor for Parkinson's disease. The GBA1 mutations L444P, N370S and many other have been shown to associate with the disease in populations with diverse background. Some GBA1 polymorphisms have a less pronounced effect, and their pathogenicity has been debated.

Genetic Alterations in Mitochondrial DNA Are Complementary to Nuclear DNA Mutations in Pheochromocytomas.

Background: Somatic mutations, copy-number variations, and genome instability of mitochondrial DNA (mtDNA) have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is scarce information about pheochromocytomas and paragangliomas (PCCs/PGLs) formation.

Material: To determine the potential roles of mtDNA alterations in sporadic PCCs/PGLs, we analyzed a panel of 26 nuclear susceptibility genes and the entire mtDNA sequence of seventy-seven human tumors, using next-generation sequencing, and compared the results with normal adrenal medulla tissues.

Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS.

Background: Enzymes of tricarboxylic acid (TCA) have recently been recognized as tumor suppressors. Mutations in the SDHB subunit of succinate dehydrogenase (SDH) cause pheochromocytomas and paragangliomas (PCCs/PGLs) and predispose patients to malignant disease with poor prognosis.

Methods: Using the human pheochromocytoma cell line (hPheo1), we knocked down SDHB gene expression using CRISPR-cas9 technology.

Association of Protective With Positive Ankylosing Spondylitis.

Objectives: To further elucidate the role of the MHC in ankylosing spondylitis by typing 17 genes, searching for independent associations and assessing the impact of sex on this male biased disease.

Methods: High-confidence two-field resolution genotyping was performed on 310 cases and 2196 controls using an concordance method. Protein-coding variants were called from next-generation sequencing reads using up to four software programs and the consensus result recorded.

Increased diagnostic sensitivity of palpation-guided thyroid nodule fine-needle aspiration cytology by BRAF V600E-mutation analysis.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and its incidence is increasing. Preoperative diagnosis is warranted in order to avoid 'two-stage' procedures that are associated with additional costs and higher radioactive iodine remnant uptake. In the setting of thyroid cancer, somatic BRAF V600E-mutations are highly specific for PTC and can be analyzed in aspirates from fine-needle aspiration cytology (FNAC).

Telomerase reverse transcriptase mutation and the p53 pathway in T1 urinary bladder cancer.

Objective: To study the telomerase reverse transcriptase (TERT) mutation and the p53 pathway in T1 urinary bladder cancer (UBC).

Materials And Methods: This prospectively performed population-based study included all patients in the Southeast Healthcare Region in Sweden with T1 UBC registered in the period 1992-2001, inclusive. Given that p53 and TERT are important factors for tumour proliferation, although their interrelationships are unknown, we assessed both the TERT and the p53 mutations.

X-chromosome variants are associated with aldosterone producing adenomas.

Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism (PA) and are characterized by constitutively producing aldosterone, which leads to hypertension. Several mutations have been identified in ion channels or ion channel-associated genes that result in APAs. To date, no studies have used a genome-wide association study (GWAS) approach to search for predisposing loci for APAs.

Autosomal recessive congenital hereditary corneal dystrophy associated with a novel mutation in two consanguineous Tunisian families.

Background: Autosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 () gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).

Methods: To identify gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.

Deletions on Chromosome Y and Downregulation of the Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients.

Background: Biological causes of sex disparity seen in the prevalence of cancer, including glioblastoma (GBM), remain poorly understood. One of the considered aspects is the involvement of the sex chromosomes, especially loss of chromosome Y (LOY).

Methods: Tumors from 105 isocitrate dehydrogenase (IDH) wild type male GBM patients were tested with droplet digital PCR for copy number changes of ten genes on chromosome Y.

Sex Disparities in Promoter Methylation and Survival in Glioblastoma: Further Evidence from Clinical Cohorts.

Introduction: Recent studies suggest an overrepresentation of promoter methylated tumors in females with wt glioblastoma (GBM) compared to males, with a subsequent better response to alkylating treatment.

Methods: To reveal sex-bound associations that may have gone unnoticed in the original analysis, we re-analyzed two previously published clinical cohorts. One was the multicenter Nordic trial of elderly patients with GBM, randomizing patients into three different treatment arms, including 203 cases with known promoter methylation status.

Activation of RAS Signalling is Associated with Altered Cell Adhesion in Phaeochromocytoma.

Phaeochromocytomas and paragangliomas (PPGLs) are neuroendocrine catecholamine-producing tumours that may progress into inoperable metastatic disease. Treatment options for metastatic disease are limited, indicating a need for functional studies to identify pharmacologically targetable pathophysiological mechanisms, which require biologically relevant experimental models. Recently, a human progenitor phaeochromocytoma cell line named "hPheo1" was established, but its genotype has not been characterised.

Do we really know who has an methylated glioma? Results of an international survey regarding use of analyses for glioma.

Background: Glioma O6-methylguanine-DNA methyltransferase () promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.

Methods: We conducted an international survey to clarify which methods are regularly used and why.

Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group.

Introduction: Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multiforme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients.

Materials And Methods: A cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study.

ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide.

Standard treatment for glioblastoma (GBM) patients is surgery and radiochemotherapy (RCT) with temozolomide (TMZ). TMZ is a substrate for ABCB1, a transmembrane drug transporter. It has been suggested that survival for GBM patients receiving TMZ is influenced by different single-nucleotide variants (SNV) of ABCB1.

A somatic mutation in CLCN2 identified in a sporadic aldosterone-producing adenoma.

Objective: To screen for CLCN2 mutations in apparently sporadic cases of aldosterone-producing adenomas (APAs).

Description: Recently, CLCN2, encoding for the voltage-gated chloride channel protein 2 (ClC-2), was identified to be mutated in familial hyperaldosteronism II (FH II). So far, somatic mutations in CLCN2 have not been reported in sporadic cases of APAs.

Novel BEST1 gene mutations associated with two different forms of macular dystrophy in Tunisian families.

Background: Epidemiological studies of hereditary eye diseases allowed us to identify two Tunisian families suffering from macular dystrophies: Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The purpose of the current study was to investigate the clinical characteristics and the underlying genetics of these two forms of macular dystrophy.

Methods: Complete ophthalmic examination was performed including optical coherence tomography, electroretinography, electrooculography and autofluoresence imaging in all patients.