New monoallelic combination of KRAS gene mutations in codons 12 and 13 in the lung adenocarcinoma.

PURPOSE: In a retrospective analysis of the prevalence of KRAS mutations in patients with advanced non-small cell lung cancer (NSCLC), we detected a unique and not earlier described case of a double combination of mutations at codons 12 and 13 of the KRAS gene in a patient with lung adenocarcinoma. MATERIAL/METHODS: To determine the molecular characteristics of the infrequent mutation and the mutational status of the KRAS gene in metastatic brain tumors in the same patient, we performed morphological and molecular tests. RESULTS: Molecular analysis of the nature of the double mutation showed that the unique combination of variants is a monoallelic mutation. This type of changes has not yet been registered in the Catalogue of Somatic Mutations in Cancer database. Molecular assessment of the KRAS mutation status in the brain metastatic site in the same patient, showed no mutations in codons 12 and 13. Moreover, we did not find mutation at exon 19 and 21 of EGFR gene, both in primary tumor as well as in secondary metastatic foci in the brain. CONCLUSIONS: The presented case shows an example of KRAS gene molecular mosaicism and heterogeneity of lung adenocarcinoma primary and metastatic tumors. Molecular heterogeneity of lung adenocarcinoma tumors can significantly affect eligibility of patients for targeted therapies.

The association of the FTO rs9939609 polymorphism with obesity and metabolic risk factors for cardiovascular diseases in Polish children.

The phenomenon of excessive body mass increase in the general population of children and adults in the past few decades and has been attributed to environmental changes, especially when superimposed on a predisposing genetic background. The fat mass and obesity-associated (FTO) gene has recently become one of the most extensively investigated genes associated with body mass. The aim of the study was to investigate the association of the FTO rs9939609 T>A single-nucleotide polymorphism with selected anthropometric and metabolic parameters and blood pressure in a large population of Polish children. A total of 968 children aged 4 to 18 years were included in the study. Genotyping was performed using a TaqMan assay. The rs9939609 marker was associated with standardised (standard deviation scores, SDSs) values of body mass, height, body mass index (BMI), waist circumference, hip circumference and arm circumference. When we compared normal-weight with obese children we observed a strong recessive predisposing effect of the A-allele (OR=2.11 95% CI: 1.50-2.99, p=2.23 x 10(-6) for AA vs. TT+AT). Univariate analysis revealed associations of the FTO gene variants with the values of blood pressure, triglycerides, fasting glucose and HOMA insulin resistance index. After taking into account SDS BMI only the association with HOMA remained statistically significant. The FTO gene polymorphism may partially explain the predisposition to obesity in the population of Polish children. The potential effect on the remaining cardiovascular risk factors seems indirect and dependent on BMI changes. The polymorphism may be independently associated with insulin resistance.

The status of BK polyomavirus replication in adult renal transplant recipients in northeastern Poland.

PURPOSE: BK polyomavirus (BKV) infection and BKV-associated nephropathy (BKVAN) are among the most important problems in renal transplantation. We aimed to determine the incidence of BK viruria, viremia, and BKVAN in renal transplant recipients in the northeastern part of Poland. METHODS: Urine and blood samples from 126 cadaveric renal transplant recipients were analyzed for BK viruria and viremia using quantitative real-time polymerase chain reaction and the patients were followed prospectively. The diagnosis of BKVAN was established on the allograft biopsy. RESULTS: Based on the BKV DNA analysis, the patients were divided into three groups: group 1 (n=89; 70.6%) without viruria or viremia, group 2 (n=24; 19.1%) with isolated viruria, and group 3 (n=13; 10.3%) with both viruria and viremia. The presence of BK viremia negatively correlated with time after the transplantation. BK viruria was associated with mycophenolate mofetil daily dose. In group 3 there were four patients (3.2%) with high viremia (>10(4) genome equivalents [gEq]/mL) and viruria (>10(7) gEq/mL) loads. Only one patient from this group developed clinical symptoms and had BKVAN in allograft biopsy. In all four cases, the maintenance immunosuppression therapy was based on tacrolimus and steroids. CONCLUSION: Prevalence of BKV infection in renal transplant recipients in the northeastern part of Poland is similar to that reported by studies from other countries. We confirm that BK viremia could be predicted by the presence of intense viruria. Time after transplantation and the type of immunosuppression strategy are the most important predictors of BK viremia and viruria in patients after renal transplantation.

A case of lupus vulgaris with rare localization diagnosed 30 years after onset.

Cutaneous tuberculosis (tuberculosis cutis) is one of the extrapulmonary forms of tuberculosis, which may affect the skin only or co-exist with tuberculosis of other organs, particularly the lungs. We describe a case of lupus vulgaris in a 72-year-old male patient with a single lesion localized on his lower extremity, developing for 30 years before correct diagnosis and previously treated with topical steroids. Bacillus infection in other organs was not detected. Diagnosis of tuberculosis was made based on personal history, clinical picture, hypersensitivity to tuberculin, histopathology and polymerase chain reaction. A multidrug therapy with rifampicin, isoniazid and pyrazinamide resulted in regression of the lesion. The common lack of knowledge about the clinical picture of cutaneous tuberculosis causes its late diagnosis and treatment.

P-selectin gene genotypes or haplotypes and cardiovascular complications in type 2 diabetes mellitus.

BACKGROUND AND AIM: Increased levels of sP-selectin, a member of the selectin family involved in the transient attachment of leukocytes to endothelial cells, are found in a number of conditions including diabetes and ischemic heart disease. A number of polymorphisms in the gene encoding P-selectin have been identified. The purpose of the present study was to explore the role of three non-synonymous P-selectin gene polymorphisms, Tyr715Pro, Asn562Asp and Ser290Asn, in determining the risk of macrovascular complications in type 2 diabetic patients. METHODS AND RESULTS: Following a cross-sectional case-control design from 837 Italian type 2 diabetics, 301 cases with at least one episode of angina pectoris (AP), acute myocardial infarction (AMI), stroke, transient ischemic attacks (TIA) or peripheral arterial disease (PAD) were compared with 536 controls free of ischemic vascular complications in the period preceding the examination. Case subjects had longer duration of diabetes at the time of examination and were older as compared with controls. Hypertension and male sex were over-represented among cases. Allele frequency and genotype distribution of the three polymorphic variants did not show any significant preferential association in groups of cases or controls. Odds ratios also indicated no effect on risk of cardiovascular disease even after adjustment for potentially confounding variables. There was a strong allelic association between Tyr715Pro and Asn562Asp (D' = -0.99, P < 0.0001). Ser290Asn was in linkage disequilibrium with Tyr715Pro (D' = 0.43, P = 0.15) and in almost complete equilibrium with Asn562Asp (D' = 0.05, P = 0.5). Haplotype phase inferred from genotypic data revealed the presence of 6 haplotypes. Global test of significance showed no difference in three marker haplotype distribution between cases and controls (P = 0.88, df = 5). CONCLUSIONS: The present study excludes a major contribution of Tyr715Pro, Asn562Asp and Ser290Asn P-selectin polymorphisms to a susceptibility to ischemic vascular complications in type 2 diabetes.