Expanding the Molecular Landscape of Androgen Insensitivity Syndrome Through Next-Generation Sequencing.

Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder caused by mutations in the androgen receptor gene (), leading to impaired androgen signaling and resulting in varying degrees of undermasculinization in individuals with a 46,XY karyotype. This study aimed to expand the molecular landscape of AIS by identifying and characterizing pathogenic variants in the gene via next-generation sequencing (NGS). Molecular diagnostics revealed eight distinct variants within the gene, two of which had not been previously described.

Report on the Effect of the Implementation of an Early Detection and Prevention of Cancer Program on Families at High Hereditary Risk-Concentrating on Patients Undergoing Genetic Diagnostics and Counseling in Central Poland.

Over a 46-month period, the objectives of the National Cancer Control Program (NCCP, pol. Narodowy Program Zwalczania Chorób Nowotworowych), coordinated by the Ministry of Health, were pursued by conducting genetic diagnostics on individuals at high risk of developing cancer. A total of 1097 individuals were enrolled in the study, leading to the identification of 128 cases of germline mutations.

The Usefulness of Cell-Based and Liquid-Based Urine Tests in Clarifying the Diagnosis and Monitoring the Course of Urothelial Carcinoma. Identification of Novel, Potentially Actionable, and Somatic Mutations.

Bladder cancer is one of the most common cancers in global statistics. One of the issues associated with this disease is the high incidence of cases with delayed diagnosis and what factors correlate with worse treatment outcomes. A possible reason for this may be the rather limited availability of non-invasive diagnostic tools.

Genotypic and Phenotypic Changes in as a Result of Cold Plasma Treatment.

We treated cells with a sublethal dose of nonequilibrium (cold) atmospheric-pressure He plasma and studied alterations in the genome of this fungus as well as changes in the phenotypic traits, such as assimilation of carbon from carbohydrates, hydrolytic enzyme activity, and drug susceptibility. There is a general problem if we use cold plasma to kill microorganism cells and some of them survive the process-whether the genotypic and phenotypic features of the cells are significantly altered in this case, and, if so, whether these changes are environmentally hazardous. Our molecular genetic studies have identified six single nucleotide variants, six insertions, and five deletions, which are most likely significant changes after plasma treatment.

Comparative analysis of 13 HPV genotypes diagnosed in urine sediment cells vs. desquamated cervical epithelial cells.

Introduction: The human papilloma virus (HPV) belongs to double-stranded, DNA circular viruses which infect the epithelial cells. The highest incidence of HPV is identified in malignant processes which affect the uterine cervix, as well as vulvar, penile, rectal and pharyngeal regions.

Goal Of Study: An attempt to find correlations between HPV incidence rates in urine sediment cells and in desquamated epithelial cells of the uterine cervix in a group of patients with frequent, recurrent cystitis.

Detection of bladder cancer in urine sediments by a hypermethylation panel of selected tumor suppressor genes.

Background: Promoter hypermethylation can be a useful biomarker for early detection and prognosis of bladder cancer, monitoring response to treatment and complement classical diagnostic procedures.

Objective: The molecular test was performed on DNA from bladder cancer cells in voided urine samples, tumor tissue DNA and normal control DNAs. We aimed to assess the diagnostic potential of epigenetic changes in urine DNA from bladder cancer cases at various clinico-pathological stages of the disease.

Diagnostics of SHOX gene rearrangement in 46,XX women with idiopathic short stature.

Introduction: The SHOX gene has been mapped at the pseudoautosomal region 1 (PAR1) of chromosomes X (Xp22.33) and Y (Yp11.32).

The risk of neoplasm associated with dysgenetic testes in prepubertal and pubertal/adult patients.

Introduction: In patients with Y-chromosome in the karyotype, partial gonadal dysgenesis and disorders of male reproductive sex organs development are usually resected in childhood because of the high risk of germ cell tumours (GCT). In patients with Y-chromosome, complete gonadal dysgenesis and female genitalia gonadectomy is performed markedly later. However, due to the relatively low number of adult patients with preserved dysgenetic gonads, the true risk of neoplasm is unknown.

[Evaluation of genomic imbalance in endometrial hyperplasia and carcinoma].

Objective: The main goal of our study was to identify the earliest and specific genetic changes which could be associated with an increased risk of neoplastic transformation in a group of patients with endometrial hyperplasia. Another goal was to characterize genetic changes associated with advanced forms of cancer.

Material And Methods: The study involved forty-four (44) female patients, including five (5) patients with no histopathologically confirmed hyperplastic features, twenty-six (26) patients with histopathologically confirmed endometrial hyperplasia, and thirteen (13) patients with diagnosed carcinoma of the endometrium.

Molecular subtyping of bladder cancer using Kohonen self-organizing maps.

Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients.

Concomitance of oncogenic HPV types, CHEK2 gene mutations, and CYP1B1 gene polymorphism as an increased risk factor for malignancy.

Introduction: Urinary bladder carcinoma ranks the fourth position in malignancy incidence rates in men (6.1%) and the 17th position in women (1.6%).

EORTC risk tables - their usefulness in the assessment of recurrence and progression risk in non-muscle-invasive bladder cancer in Polish patients.

Introduction: The assessment of risk of recurrence and progression of bladder cancer (BC) is still rather difficult. We decided to check the rates of the changes mentioned above in the group of the Polish patients after a year-long observation and next to compare them with the results calculated in the European Organisation of Research and Treatment of Cancer (EORTC) risk tables.

Methods: The tested group consisted of 91 patients who underwent transurethral resection of bladder tumour (TURBT).

A novel mutation (c.T3816 > C) in the androgen receptor gene in a 46,XY female patient with androgen insensitivity syndrome.

Introduction: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD), and are associated with a variety of phenotypes ranging from phenotypic women (Complete Androgen Insensitivity Syndrome or CAIS) to milder degrees of undervirilisation (Partial Androgen Insensitivity Syndrome or PAIS) or men with infertility only (Mild Androgen Insensitivity Syndrome or MAIS). In this paper, we present the results of clinical, endocrine and molecular trials in a patient hospitalised because of primary amenorrhoea with typical phenotype of CAIS.

Material And Methods: The main objective of this study was to determine the molecular cause of androgen insensitivity syndrome in a 46,XY female patient.

A novel mutation (c. 341A>G) in the SRY gene in a 46,XY female patient with gonadal dysgenesis.

SRY (sex-determining region Y) gene, MIM 480000, NM_005634) is crucial for sex differentiation which encodes the protein responsible for initiating testis differentiation. SRY mutations are associated with the presence of XY gonadal dysgenesis symptoms. We studied a 46,XY female patient with primary amenorrhoea and negative family history.

Polymorphic variants of H-RAS protooncogene and their possible role in bladder cancer etiology.

Introduction: H-RAS gene is a protooncogene encoding p21ras, a small protein with GTPase activity. This protein is a component of many signaling cascades, while mutations in H-RAS gene are often found in urinary bladder cancer and leads to continuous transmission of signals stimulating cancer cell growth and proliferation. The T81C polymorphism of H-RAS gene is a SNP, which, although does not seem to impair p21ras protein structure and function, may contribute to the development of bladder cancer.

Prenatal diagnosis of rare fetal anomalies--a case report.

Hereby we present a case of a pregnancy in which careful dysmorphology of the fetus in subsequent sonographic evaluation resulted in detection of a very rare anomaly. It allowed explanation of the fetal phenotype, compared then with that of the newborn and estimation of genetic risk for the next pregnancies in this family.

Significance of CDKN2A gene A148T variant in patients with bladder cancer.

Objectives: The A148T polymorphism of CDKN2A gene is observed in various neoplasms with the incidence rate of 3-35%, however, rather little is known either about the frequency of its occurrence or of its significance in urinary bladder carcinoma.

Materials And Methods: DNA was isolated from blood of 156 patients with urinary bladder carcinoma (130 men). In histopathology, 84 cases were classified as G1, 42 as G2, and 30 as G3.

Detection of loss of heterozygosity in patients with urinary bladder carcinoma: neoplastic tissue vs. urine sediment cells.

Introduction: Loss of heterozygosity (LOH) is frequently observed in urinary bladder neoplasms. In the reported study, an attempt was undertaken to determine the loss of heterozygosity of TP53(17p13), RB1(13q14), CDKN2A/ ARF(9p21) genes in DNA from neoplastic tissue, collected from patients with diagnosed urinary bladder carcinoma, and to compare the results with those of LOH evaluation in DNA isolated from urine sediment cells.

Material And Methods: After isolation, DNA was amplified (PCR) by means of primers to five polymorphic microsatellite markers, the products being then separated on agarose gel.

P53 mutations in urinary bladder cancer patients from Central Poland.

The present study aimed at detection of P53 gene mutations in cells of urinary bladder neoplasms, as the mutations may be regarded as an independent prognostic factor for progression and recurrence of tumours. In the study, 82 patients with clinically diagnosed urinary bladder tumour were included. The control was composed of DNA samples from urine and blood of 202 healthy patients.

[Population genetics of 17 Y chromosome STR loci in a diverse ethnically groups of Polish citizens].

Introduction: The Y-chromosome has become a powerful tool in identification and characterization of male DNA in forensic analysis. If Y-STRs are used in forensic analysis it is important to establish a meaning of a match (how frequent a particular haplotype has been observed in a population). In literature higher haplotype frequency values were observed in samples from small and isolated populations such as Gypsies.

[Genetic polymorphisms of 10 STR (AmpFlSTR SGM Plus system) loci in Gypsy population from Poland].

Introduction: The aim of the paper was to create a database of the allele distribution at 10 STR loci (D3S1358, vWA, D16S539, D2S1338, D8S1179, D21S11, D18S51, D19S433, TH01, FGA).

Material And Methods: The DNA were isolated from samples collected from 222 unrelated individuals of the Gypsy population from Poland. Amplification was performed using a commercial multiplex FlSTR SGM Plus kit.

Application of multiplex FISH, CGH and MSSCP techniques for cytogenetic and molecular analysis of transitional cell carcinoma (TCC) cells in voided urine specimens.

Multiplex FISH (UroVysion), Comparative Genomic Hybridization (CGH), and Multitemperature Single-Strand Conformation Polymorphism (MSSCP) were applied for non-invasive diagnosis and prognosis of bladder cancer. The UroVysion test was positive in 80% of patients with pT1 and in 100% of patients with either pT2 or pT3 tumours. Tumours with pT3T4 stages were characterized by high numbers of chromosomal imbalances, detected by CGH.

A mutation c.C2812T in the androgen receptor gene resulting in Pro817Leu substitution may affect dimerization of the androgen receptor and result in androgen insensitivity syndrome.

Objective: To conduct clinical, genetic, and molecular diagnostics of two sisters with typical symptoms of complete androgen insensitivity syndrome.

Design: Case report.

Setting: Research laboratory at a university of medical science.

Chromosomal mosaicism on amniotic interphase nuclei detected by multiprobe FISH.

So far classical prenatal detection of chromosome aberrations has been limited to the evaluation of metaphase by means of time-consuming cytogenetic techniques. The MultiVision PGT test enables a simultaneous detection of aneuploidies of chromosomes 13,18, 21, X, and Y, even 24 h after amniocentesis. In the presented case, this test detected prenatally a chromosomal mosaicism 69,XYY[35]/46,XY[65].