miR-34a-FOXP1 Loop in Ovarian Cancer.

Ovarian cancer (OC) is the main cause of gynecological cancer mortality in most developed countries. microRNA (miR) expression dysregulation has been highlighted in human cancers, and miR-34a is found to be downregulated and associated with inhibition of tumor growth and invasion in several malignancies, including OC. The winged helix transcription factor forkhead box P1 (FOXP1) is reported as either an oncogene or tumor suppressor in various cancers. This study aimed to elucidate potential clinical and biological associations of miR-34a and transcription factor FOXP1 in OC. We investigated nine OC patients' blood samples and two OC cell lines (SKOV-3 and OVCAR-3) using quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) to determine both miR-34a and FOXP1 expressions. We have found that miR-34a and FOXP1 are reversely correlated in both in vitro and in vivo. Inhibition of miR-34a transiently led to upregulation of FOXP1 mRNA expression and increased cellular invasion in vitro. Our data indicate that miR-34a could be a potential biomarker for improving the diagnostic efficiency of OC, and miR-34a overexpression may reduce OC pathogenesis by targeting FOXP1.

Evaluation of 5-HTTLPR Gene Polymorphism and Resilience Components on the Development of Psychopathology in Adolescent Sexual Abuse Cases.

INTRODUCTION: More than one-fourth adolescents are exposed to unexpected frightening experiences and traumas until adulthood. In this study, we aimed to determine the potential role of serotonin transporter (5-HTT) gene polymorphism regarding resilience factors in the symptom variability of individuals exposed to sexual abuse. METHODS: Adolescents aged 11-17 years, who were admitted to the Marmara University Child Psychiatry Outpatient Clinic Forensic division with sexual abuse experience history, were informed about the research, and volunteers were included in the study. Turkish versions of "Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (K-SADS-PL)" was used to assess the psychopathology and functionality. The evaluation of participants also included self-reports based on "Eysenck Personality Inventory" and "Ways of Coping Inventory" for reflecting the resilience domain. RESULTS: The sample included 16 girls (88.9%) and 2 boys (11.1%), and the mean (±standard deviation) age was 14.58±1.97 years. Genotyping of the insertion/deletion polymorphism (5-HTTLPR) in the 5-HTT gene's transcriptional control zone was established, and 8 participants (44.4%) were determined to be of the LL genotype, while 7 (38.8%) were LS and 3 (16.6%) were SS carriers. Considering the relationship between coping styles regarding resilience and genetic variants, 87.5% of participants (n=7) exhibiting problem-focused coping style were determined found to carry the LL allele, while 90% (n=9) who exhibited emotion-focused coping styles were the SS-LS allele carriers (p=0.003). CONCLUSION: Our findings suggest that 5-HTTLPR gene polymorphism has a significant impact on the formation of coping styles. More studies are needed to determine other factors involved in the complex relationship between 5-HTTLPR gene polymorphism and development of psychopathology.

The effect of polymorphic metabolism enzymes on serum phenytoin level.

Phenytoin has a widespread use in epilepsy treatment and is mainly metabolized by hepatic cytochrome P450 enzymes (CYP). We have investigated CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3 allelic variants in a Turkish population of patients on phenytoin therapy. Patients on phenytoin therapy (n = 102) for the prevention of epileptic seizures were included. Polymorphic alleles were analyzed by restriction fragment length polymorphism method. Serum concentrations of phenytoin were measured by fluorescence polarization immune assay method. The most frequent genotype was detected for CYP2C9 wild-type alleles (78.43 %), whereas CYP2C19*2/*2 (5.88 %) was the least frequent genotype group. According to the classification made with both enzyme polymorphisms, CYP2C9*1/*1-CYP2C19*1/*1 (G1: 41.17 %) genotype group was the most frequent whereas CYP2C9*1/*2-CYP2C19*1/*3 (G7: 0.98 %) was the least frequent one. The highest mean phenytoin level (27.95 ± 1.85 µg/ml) was detected in the G8 genotype group (CYP2C9*1/*3-CYP2C19*2/*3) and the G1 genotype group showed the lowest mean phenytoin level (7.43 ± 0.73 µg/ml). The mean serum concentration of phenytoin of the polymorphic patients with epilepsy was higher than that for the wild-type alleles both in the monotherapy and polytherapy patients. These results show the importance of the genetic polymorphism analysis of the main metabolizing enzyme groups of phenytoin for the dose adjustment.

A novel heterozygous deletion within the 3' region of the PAX6 gene causing isolated aniridia in a large family group.

Paired box gene 6 (PAX6) is the causative gene of aniridia. It is a dominantly inherited eye abnormality characterized by partial or complete absence of the iris. The PAX6 gene is located on chromosome 11p13 and contains 14 exons. It is expressed mainly in the developing eye and central nervous system. Submicroscopic copy number variations are common in the human genome. Submicroscopic deletions may cause several human diseases, either by disrupting coding sequences or by eliminating regulatory elements essential for expression of the gene in question. Over the past several years, array-based comparative genomic hybridization has become an increasingly useful tool for both identifying normal cytogenetic variations and characterizing chromosomal abnormalities associated with developmental delays and cancer. Our results support the notion that assessing copy number variation of the PAX6 gene itself and also of flanking regions, may contribute to the molecular diagnosis of aniridia.

New candidate chromosomal regions for chordoma development.

BACKGROUND: Chordomas are rare, slow growing, infiltrative tumors thought to arise from vestigial or ectopic notochord. Chordoma can occur along the axial skeleton, predominantly in the sphenooccipital, vertebral, and sacrococcygeal regions. Although most chordomas are sporadic, familial cases have also been reported. The most common molecular cytogenetic abnormalities in these tumors are monosomy of chromosome 1 and gain of chromosome 7. In addition, a variety of other chromosomal changes, which are associated with losses and gains of different chromosomes, have also been described in chordomas, such as 1q, 2p, 3p, 5q, 9p, 10, 12q, 13q, 17, and 20q. METHODS: In this study, using molecular cytogenetics (iFISH), we have studied 1p36, 1q25, 3p13-p14, 7q33, 17p13.1 (p53 gene locus), 2p13 (TGF-alpha locus), 6p12 (VEGF locus), and 4q26-q27 (bFGF/FGF2 locus) loci in chordoma tissues from seven patients with 7 primary tumors and 11 recurrences. RESULTS: We found that chromosomes 1p36, 1q25, 2p13, and 7q33 are affected in primary chordomas, and these aberrations persist in recurrences. However, the chromosome 6p12 aberration was seen only in primary chordomas, but not in recurrences, indicating that this locus may be associated with chordoma genesis. CONCLUSIONS: Our descriptive data from interphase FISH analyses suggest that future studies should incorporate a larger number of patients and should focus on identifying the candidate genes in chordoma pathogenesis. Such studies may use a whole-genomic approach, in addition to the regions identified in this study and others.

A patient with hypopituitarism and isochromosome 18q mosaicism.

AIMS: Patients with isochromosome 18 [i(18q)] have features of both trisomy 18 and deletion of 18p [del(18p)] syndromes. Although, hypopituitarism has been reported in patients with del(18p) syndrome, it has not been described in patients with i(18q) syndrome previously. We describe a case with i(18q)/del(18p) mosaicism associated with a novel finding of hypopituitarism. METHODS: Clinical characteristics of the patient have been discussed in the light of the literature. RESULTS: The patient had dysmorphic findings that are predominantly seen in del(18p) syndrome such as low nasal bridge, wide mouth, large ears, high forehead, hypopigmentation, upturned nostrils and hypopituitarism (TSH, ACTH, and GH deficiencies, and pituitary hypoplasia on magnetic resonance imaging). In addition, she also had upturning of upper lip and seizures, which are features of trisomy 18 syndrome. CONCLUSIONS: In agreement with the previous clinical reports, this case further supports the presence of a factor, which is involved in pituitary development and/or function, on the short arm of chromosome 18.

The Mckusick-Kaufman syndrome: report of a case with some associations.

McKusick-Kaufman syndrome (MKS) is a rare autosomal recessive condition consisting of congenital hydrometrocolpos, polydactyly and congenital heart defect. We present a female stillborn, the product of non-consanguineous parents, who presented postaxial polydactyly on both feet, micrognathia and marked abdominal distension. Postmortem examination revealed bicornuated cystic uterus and intestinal malrotation. She also had flat left kidney and left hydroureter due to compression by the cystic mass.