Cytogenomic epileptology.

Molecular cytogenetic and cytogenomic studies have made a contribution to genetics of epilepsy. However, current genomic research of this devastative condition is generally focused on the molecular genetic aspects (i.e.

A spectrum of BRCA1 and BRCA2 germline deleterious variants in ovarian cancer in Russia.

Purpose: Pathogenic variants (PVs) in BRCA1 and BRCA2 genes are essential biomarkers of an increased breast and ovarian cancer risk and tumor sensitivity to poly ADP ribose polymerase inhibitors. In Russia, eight PVs were thought to be the most common, among which BRCA1 c.5266dup is the most frequently identified one.

Multiplex Droplet Digital PCR Assay for Detection of and Genes Amplification in Non-Small Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC), a subtype of lung cancer, remains one of the most common tumors with a high mortality and morbidity rate. Numerous targeted drugs were implemented or are now developed for the treatment of NSCLC. Two genes, and , are among targets for these specific therapeutic agents.

Klinefelter syndrome mosaicism in boys with neurodevelopmental disorders: a cohort study and an extension of the hypothesis.

Background: Klinefelter syndrome is a common chromosomal (aneuploidy) disorder associated with an extra X chromosome in males. Regardless of numerous studies dedicated to somatic gonosomal mosaicism, Klinefelter syndrome mosaicism (KSM) has not been systematically addressed in clinical cohorts. Here, we report on the evaluation of KSM in a large cohort of boys with neurodevelopmental disorders.

Turner's syndrome mosaicism in girls with neurodevelopmental disorders: a cohort study and hypothesis.

Background: Turner's syndrome is associated with either monosomy or a wide spectrum of structural rearrangements of chromosome X. Despite the interest in studying (somatic) chromosomal mosaicism, Turner's syndrome mosaicism (TSM) remains to be fully described. This is especially true for the analysis of TSM in clinical cohorts (e.

Overall Survival of Patients With -Positive Metastatic Non-Small-Cell Lung Cancer in the Russian Federation: Nationwide Cohort Study.

Purpose: The overall survival (OS) results in patients with -positive metastatic non-small-cell lung cancer (NSCLC) have rarely been reported. The aim of this prospective-retrospective cohort study was to obtain real-world data on the use of crizotinib or chemotherapy in patients with -positive metastatic NSCLC in Russia.

Patients And Methods: Patients with epidermal growth factor receptor-negative metastatic NSCLC were screened in 23 cancer centers.

Mosaic Brain Aneuploidy in Mental Illnesses: An Association of Low-level Post-zygotic Aneuploidy with Schizophrenia and Comorbid Psychiatric Disorders.

Background: Postzygotic chromosomal variation in neuronal cells is hypothesized to make a substantial contribution to the etiology and pathogenesis of neuropsychiatric disorders. However, the role of somatic genome instability and mosaic genome variations in common mental illnesses is a matter of conjecture.

Materials And Methods: To estimate the pathogenic burden of somatic chromosomal mutations, we determined the frequency of mosaic aneuploidy in autopsy brain tissues of subjects with schizophrenia and other psychiatric disorders (intellectual disability comorbid with autism spectrum disorders).

Highly Sensitive and Reliable Detection of EGFR Exon 19 Deletions by Droplet Digital Polymerase Chain Reaction.

Background: Analysis of EGFR mutations is becoming a routine clinical practice but the optimal EGFR mutation testing method is still to be determined.

Methods: We determined the nucleotide sequence of deletions located in exon 19 of the EGFR gene in lung tumor samples of patients residing in different regions of Russia (153 tumor DNA specimens), using Sanger sequencing. We developed a droplet digital polymerase chain reaction assay capable of detecting all common EGFR deletions in exon 19.

Detection of ALK rearrangements in 4002 Russian patients: The utility of different diagnostic approaches.

Background: Clinical guidelines highly recommended the detection of potentially targetable genetic aberrations such as anaplastic lymphoma kinase (ALK) rearrangements in patients with non-small cell lung cancer (NSCLC). Few methods, such as the ALK break apart FISH assay and IHC for ALK protein, are approved for routine diagnostics. However, some challenges exist in selecting the most reliable, robust and cost-effective algorithm, especially for large-scale screening of NSCLC patients.

Distribution of EGFR Mutations in 10,607 Russian Patients with Lung Cancer.

Introduction: This study was aimed to evaluate distribution of epidermal growth factor receptor (EGFR) mutations in a large series of Russian lung cancer (LC) patients.

Methods: 10,607 LC samples were considered for EGFR analysis; EGFR status was successfully determined in 10,426 cases (98.3 %), indicating relatively low failure rate.

5p13.3p13.2 duplication associated with developmental delay, congenital malformations and chromosome instability manifested as low-level aneuploidy.

Recent developments in molecular cytogenetics allow the detection of genomic rearrangements at an unprecedented level leading to discoveries of previously unknown chromosomal imbalances (zygotic and post-zygotic/mosaic). These can be accompanied by a different kind of pathological genome variations, i.e.

Sensitive genotyping of somatic mutations in the EGFR, KRAS, PIK3CA, BRAF genes from NSCLC patients using hydrogel biochips.

Targeted inhibitors of the epidermal growth factor receptor (EGFR) are used for the treatment of non-small cell lung cancer (NSCLC). Somatic mutations in the EGFR gene and key effectors of the EGFR-signaling pathway (KRAS, BRAF, PIK3CA) are associated with sensitivity to these drugs. We developed a highly sensitive LUNG CANCER (LC)-biochip approach for the detection of the most common EGFR, KRAS, PIK3CA, and BRAF gene mutations.

Immunohistochemistry, fluorescence in situ hybridization, and reverse transcription-polymerase chain reaction for the detection of anaplastic lymphoma kinase gene rearrangements in patients with non-small cell lung cancer: potential advantages and methodologic pitfalls.

Context: Echinoderm microtubule-associated protein-like 4 gene (EML4) and anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of tumorigenesis in approximately 3% to 5% of patients with non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib. However, no complete agreement regarding the best diagnostic test for identification of ALK rearrangements has been achieved yet.

Objective: To investigate the concordance, sensitivity, and specificity of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription-polymerase chain reaction (RT-PCR) for detection of ALK rearrangements.

Xq28 (MECP2) microdeletions are common in mutation-negative females with Rett syndrome and cause mild subtypes of the disease.

Background: Rett syndrome (RTT) is an X-linked neurodevelopmental disease affecting predominantly females caused by MECP2 mutations. Although RTT is classically considered a monogenic disease, a stable proportion of patients, who do not exhibit MECP2 sequence variations, does exist. Here, we have attempted at uncovering genetic causes underlying the disorder in mutation-negative cases by whole genome analysis using array comparative genomic hybridization (CGH) and a bioinformatic approach.

A deletion polymorphism in glutathione-S-transferase mu (GSTM1) and/or theta (GSTT1) is associated with an increased risk of toxicity after autologous blood and marrow transplantation.

Toxicity after blood and marrow transplantation (BMT) has interindividual variability that may be explained by common genetic polymorphisms in critical pathways. The glutathione-S-transferase (GST) isoenzymes detoxify the reactive oxygen species generated by chemotherapy agents and radiation. We investigated whether deletion polymorphisms in 2 GST genes (GSTM1 and GSTT1) were associated with toxicity after autologous or allogeneic BMT.

Fetal and perinatal outcomes in type 1 diabetes pregnancy: a randomized study comparing insulin aspart with human insulin in 322 subjects.

Objective: The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy.

Study Design: This was a randomized, parallel, open-label, controlled, multicenter, multinational study. Subjects were pregnant (gestational age; <10 weeks) or planning pregnancy at enrollment.

The schizophrenia brain exhibits low-level aneuploidy involving chromosome 1.

Objective: Genetic instability manifested as loss or gain of whole chromosomes (aneuploidy) is a newly described feature of the human brain. Aneuploidy in the brain was hypothesized to be involved in schizophrenia pathogenesis. To gain further insights into the relationship between aneuploidy in the brain and schizophrenia pathogenesis, a molecular-cytogenetic study of chromosome 1 aneuploidy was performed.

Aneuploidy and confined chromosomal mosaicism in the developing human brain.

Background: Understanding the mechanisms underlying generation of neuronal variability and complexity remains the central challenge for neuroscience. Structural variation in the neuronal genome is likely to be one important mechanism for neuronal diversity and brain diseases. Large-scale genomic variations due to loss or gain of whole chromosomes (aneuploidy) have been described in cells of the normal and diseased human brain, which are generated from neural stem cells during intrauterine period of life.