The role of next-generation sequencing in the examination of signaling genes in Brca1/2-negative breast cancer cases.

INTRODUCTION: Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and classified genetic variations in non-BRCA signaling genes and investigate the underlying genetic causes of susceptibility to breast cancer. METHODS: Ninety-six patients without pathogenic variants in the BRCA1/2 genes who met the inclusion criteria were enrolled in the study, and 34 genes were analyzed using next-generation sequencing (NGS) for genetic analysis. RESULTS: Based on the ClinVar database or American College of Medical Genetics criteria, a total of 55 variants of 16 genes were detected in 43 (44.8%) of the 96 patients included in the study. The pathogenic variants were found in the TP53, CHEK2, and RET genes, whereas the likely pathogenic variants were found in the FGFR1, FGFR3, EGFR, and NOTCH1 genes. CONCLUSION: The examination of signaling genes in patients who met the established criteria for hereditary breast cancer but were negative for BRCA1/2 pathogenic variants provided additional information for approximately 8% of the families. The results of the present study suggest that NGS is a powerful tool for investigating the underlying genetic causes of occurrence and progression of breast cancer.

The diagnostic importance of pathogenic variants and variant coexistence determined by NGS-based liquid biopsy approach in patients with lung adenocarcinoma.

BACKROUND: Identification of driver mutations and rapid detection of genetic changes in lung cancer are critical in the management of the disease. Genetic structures of tumor tissues tend to change constantly and the possibility of emergence of new pathogenic variants that will create resistance to treatment. Liquid biopsy analysis has been one of the most effective approaches used to monitor and identify individual genetic changes. METHODS: In this study, TP53, EGFR, MET, ALK, PIK3CA, MAP2K, ERBB2 and ROS genes in cf DNA samples of 324 patients with lung adenocarcinoma were screened for genetic variations by NGS method. Analysis of the data showed that there were a total of 755 variations in 324 patients. RESULTS: Pathogenic and possibly pathogenic variations were identified in 178 patients (54.9%) on TP53, 118 (36.4%) on EGFR, 55 (17.0%) on MET, 46 (14.2%) on ALK, 39 (12.0%) on MAP2K, 6 (1.9%) on ERBB2 and in 2 (0,6%) patients ROS genes. The detailed variant data of the genes included in the study were compared with the patients' stage status, metastasis status, smoking, age distribution and life span data, and the presence of possible significant relationships and candidate biomarkers for the molecular pathogenesis of the disease were investigated. CONCLUSION: As a result of data analysis, genetic changes associated with metastasis and adenocarcinoma formation were identified. It has been shown that variations identified in TP53, PIK3CA, MAP2K1 and EGFR genes can play critical roles in the pathogenesis and development of the disease.

TP53, EGFR and PIK3CA gene variations observed as prominent biomarkers in breast and lung cancer by plasma cell-free DNA genomic testing.

Use of plasma cell-free DNA genomic testing, also know as liquid biopsy, reveals information for early detection and monitoring of solid tumors. Our study reports the analysis of 113 lung and 18 breast cancer patients using commercially available platforms. Lung and breast cancer panel hotspot regions on the genes were investigated. There was a significant increase in isolation efficiency with very fresh blood samples of at least 15 millilitres which were processed in minutes. TP53 gene variations were detected in both types of tumors. Additionally, associations were found for EGFR variations in lung tumors and PIK3CA variations in breast tumors. Mutation assessment of these three genes are recommended as useful biomarkers for predictive studies, to follow up tumor growth and for personalized treatment. Mutations observed in this study warrant further investigation for follow up studies and may justify expression studies. However, in our subsequent studies, we intensify our tumor profiling strategy with other methods. However in terms of true personalized medicine,future plans would include repeating these studies with ctDNA size analysis and methylation analysis of the non-coding region in the individual tumors.

Molecular signatures of chronic periodontitis in gingiva: A genomic and proteomic analysis.

BACKGROUND: To elucidate molecular signatures of chronic periodontitis (CP) using gingival tissue samples through omics-based whole-genome transcriptomic and whole protein profiling. METHODS: Gingival tissues from 18 CP and 25 controls were analyzed using gene expression microarrays to identify gene expression patterns and the proteins isolated from these samples were subjected to comparative proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data from transcriptomics and proteomics were integrated to reveal common shared genes and proteins. RESULTS: The most upregulated genes in CP compared with controls were found as MZB1, BMS1P20, IGLL1/IGLL5, TNFRSF17, ALDH1A1, KIAA0125, MMP7, PRL, MGC16025, ADAM11, and the most upregulated proteins in CP compared with controls were BPI, ITGAM, CAP37, PCM1, MMP-9, MZB1, UGTT1, PLG, RAB1B, HSP90B1. Functions of the identified genes were involved cell death/survival, DNA replication, recombination/repair, gene expression, organismal development, cell-to-cell signaling/interaction, cellular development, cellular growth/proliferation, cellular assembly/organization, cellular function/maintenance, cellular movement, B-cell development, and identified proteins were involved in protein folding, response to stress, single-organism catabolic process, regulation of peptidase activity, and negative regulation of cell death. The integration and validation analysis of the transcriptomics and proteomics data revealed two common shared genes and proteins, MZB1 and ECH1. CONCLUSION: Integrative data from transcriptomics and proteomics revealed MZB1 as a potent candidate for chronic periodontitis.

Low frequency of HLA-B27 in ankylosing spondylitis and its relationship with clinical findings in patients from Turkey.

OBJECTIVE: Human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis (AS). However, the association between clinical findings and HLA-B27 vary in terms of geographic area. This study aimed to determine the frequency of HLA-B27 positivity and its relationship with clinical findings. MATERIAL AND METHODS: All subjects fulfilling the modified New York diagnosis criteria for AS enrolled in study. The demographic data and histories of the patients were collected retrospectively from patient files. Polymerase chain reaction-based HLA-B27 analysis of all cases was performed. RESULTS: The male to female ratio was 2.5, and mean age of disease onset was 28.3 years. HLA-B27 positivity was detected in 115 patients (70%). Although there was no significant connection between the clinical findings and HLA-B27 positivity, there was a positive relationship between the presence of syndesmophytes and HLA-B27 positivity (p=0.044). The number of patients treated with anti-tumor necrosis factor was higher in the HLA-B27-positive group; however, the difference was not significant (39.1% and 28.9%, respectively). More patients were treated with anti-tumor necrosis factor in the HLA-B27-positive group than in the HLA-B27-negative group; however, the difference was not significant (39.1% and 28.9%, respectively). CONCLUSION: Compared with northern Europe, HLA-B27-positive rate of patients with AS has been shown to be lower in Turkey. Except for the presence of syndesmophytes, there was not a statistically significant relationship between HLA-B27 positivity and clinical and radiologic findings.

Gene-Expression Profiles in Generalized Aggressive Periodontitis: A Gene Network-Based Microarray Analysis.

BACKGROUND: In this study, molecular biomarkers that play a role in the development of generalized aggressive periodontitis (GAgP) are investigated using gingival tissue samples through omics-based whole-genome transcriptomics while using healthy individuals as background controls. METHODS: Gingival tissue biopsies from 23 patients with GAgP and 25 healthy individuals were analyzed using gene-expression microarrays with network and pathway analyses to identify gene-expression patterns. To substantiate the results of the microarray studies, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to assess the messenger RNA (mRNA) expression of MZB1 and DSC1. The microarrays and qRT-PCR resulted in similar gene-expression changes, confirming the reliability of the microarray results at the mRNA level. RESULTS: As a result of the gene-expression microarray studies, four significant gene networks were identified. The most upregulated genes were found as MZB1, TNFRSF17, PNOC, FCRL5, LAX1, BMS1P20, IGLL5, MMP7, SPAG4, and MEI1; the most downregulated genes were found as LOR, LAMB4, AADACL2, MAPT, ARG1, NPR3, AADAC, DSC1, LRRC4, and CHP2. CONCLUSIONS: Functions of the identified genes that were involved in gene networks were cellular development, cell growth and proliferation, cellular movement, cell-cell signaling and interaction, humoral immune response, protein synthesis, cell death and survival, cell population and organization, organismal injury and abnormalities, molecular transport, and small-molecule biochemistry. The data suggest new networks that have important functions as humoral immune response and organismal injury/abnormalities. Future analyses may facilitate proteomic profiling analyses to identify gene-expression patterns related to clinical outcome.

Deregulated Levels of the NF-κB1, NF-κB2, and Rel Genes in Ukrainian Patients with Leukemia and Lymphoma in the Post-Chernobyl Period.

OBJECTIVE: Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period. MATERIALS AND METHODS: We analyzed gene expression levels of NF-κB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin's lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using real-time polymerase chain reaction. RESULTS: Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated. CONCLUSION: These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions.

A CGH array study in nonsyndromic (primary) autism patients: deletions on 16p13.11, 16p11.2, 1q21.1, 2q21.1q21.2, and 8p23.1.

BACKGROUND/AIM: To detect specific molecular changes of DNA level in primary autism patients by using whole genome CGH array technology. MATERIALS AND METHODS: A cohort of 35 primary autism patients received clinical genetic testing by using an oligonucleotide-based CGH array platform to test for submicroscopic genomic deletions and duplications. Fluorescent in situ hybridization was performed in seven patients for confirmation of the results. RESULTS: We found 16p13.11 deletion in thirteen patients, 16p11.2 deletion in twelve patients, 1q21.1 deletion in ten patients, 2q21.1q21.2 deletion in eight patients, and 8p23.1 deletion in seven patients. CONCLUSION: Our study indicates that genes in 16p13.11, 16p11.2, 1q21.1, 2q2l.1q21.2, and 8p23.1 loci are potential predisposition and new suspicious regions for primary autism. Deletion's in these regions should be investigated in further studies to understand pathogenesis of primary autism.

Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study.

INTRODUCTION: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39. METHODS: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR. RESULTS: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings. DISCUSSION AND CONCLUSION: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.

Investigation of the diagnostic value of chromosome analysis and bacterial artificial chromosome-based array comparative genomic hybridization in prenatal diagnosis.

BACKGROUND/AIM: To investigate the diagnostic value of bacterial artificial chromosome (BAC)-based array comparative genomic hybridization (CGH) and chromosome analysis in prenatal diagnosis. MATERIALS AND METHODS: This study included the chromosome analysis and BAC-based array CGH analysis of 140 amniocentesis samples with prenatal diagnosis indications. RESULTS: Karyotype analysis showed trisomy 21 in 4 patients, trisomy 18 in 5 patients, monosomy X in 1 patient, and other anomalies in 3 patients. The BAC-based array CGH analysis showed 4 patients with trisomy 21, 4 patients with trisomy 18, and 1 patient with monosomy X as a numerical chromosome anomaly, while partial duplication was observed in chromosome 14 in 1 case as a structural anomaly. CONCLUSION: The array CGH is the most effective method available to complement cases where chromosome analysis, a gold standard in prenatal diagnosis, proves to be insufficient. Considering the inherent limitations of both methods, complementary features should be introduced in order to be able to give the most accurate data at the right time.

Identification of ApoA1, HPX and POTEE genes by omic analysis in breast cancer.

Breast cancer is the most common cancer among women and accounts for 23% of all female types of cancers. It is well recognized that breast cancer represents a heterogeneous group of tumors, and the molecular events involved in the progression to cancer remain undetermined. Moreover, available prognostic and predictive markers are not sufficient for the accurate determination of the risk for many breast cancer patients. Thus, it is necessary to discover new molecular markers for accurate prediction of clinical outcome and individualized therapy. In the present study, we performed omics-based whole-genome trancriptomic and whole proteomic profiling with network and pathway analyses of breast tumors to identify gene expression patterns related to clinical outcome. A total of 20 samples from tumors and 14 normal appearing breast tissues were analyzed using both gene expression microarrays and LC-MS/MS. We identified 585 downregulated and 413 upregulated genes by gene expression microarrays. Among these genes, HPX, POTEE and ApoA1 were the most significant genes correlated with the proteomic profile. Our data revealed that these identified genes are closely related to breast cancer and may be involved in robust detection of disease progression.

The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS)-Exposed Mice.

Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris water maze (MWM) tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience.

The effect of first chromosome long arm duplication on survival of endometrial carcinoma.

OBJECTIVE: The aim of this study is to investigate the effect of first chromosome long arm duplication (dup(1q)) in cases with endometrial carcinoma detected with array based comperative genomic hybridization (aCGH) on survival from the cancer. MATERIALS AND METHODS: A total of 53 patients with the diagnosis of endometrial carcinom due to endometrial biopsy and who have been operated for this reason have been allocated in the study. Frozen section biopsy and staging surgery have been performed for all the cases. Samples obtained from the tumoral mass have been investigated for chromosomal aberrations with aCGH method. Kaplan-Meier and Cox-regression analysis have been performed for survival analysis. RESULTS: Among 53 cases with endometrial carcinomas, dup(1q) was diagnosed in 14 (26.4%) of the cases. For the patient group that has been followed-up for 24 months (3-33 months), dup(1q) (p=.01), optimal cytoreduction (p<.001), lymph node positivity (p=.006), tumor stage >1 (p=.006) and presence of high risk tumor were the factors that were associated with survival. Cox-regression analysis has revealed that optimal cytoreduction was the most important prognostic factor (p=.02). CONCLUSION: Presence of 1q duplication can be used as a prognostic factor in the preoperative period.

Effects of curcumin on global gene expression profiles in the highly invasive human breast carcinoma cell line MDA-MB 231: A gene network-based microarray analysis.

Curcumin, or diferuloylmethane, is a major chemical component of turmeric (Curcuma longa Linn.) that has been consumed as a dietary spice through the ages. This yellow-colored polyphenol has a notably wide range of beneficial properties, including anti-inflammatory, antioxidant, antitumoral, anti-invasive and anti-metastatic activity. In the present study, microarray gene expression analysis was applied to identify the curcumin-regulated genes in a highly invasive human breast carcinoma cell line (MDA-MB 231). Cells were cultured with curcumin (20 µM) for 24 h; total RNA was isolated and hybridized to Whole Human Genome Microarray slides. Gene set enrichment analyses on our whole genome expression data revealed downregulation of the EGF pathway elements following curcumin treatment. Furthermore, gene network analysis identified a significantly relevant network among the differentially expressed genes, centered on the EGR1 and FOS genes. The members of these pathways and networks play an essential role in the regulation of cancer cell growth and development; the majority exhibited decreased expression levels following treatment with curcumin. These observations suggest that curcumin is an excellent candidate for the prevention and treatment of breast cancer.

High Throughput FISH Analysis: A New, Sensitive Option For Evaluation of Hematological Malignancies.

OBJECTIVE: The aim of this study was to determine the efficiency of the high throughput FISH analysis (HTFA) method for detecting genetic alterations in hematological malignancies, which is a new bacterial artificial chromosome array-based approach. MATERIALS AND METHODS: We performed a HTFA study of bone marrow aspiration and peripheral blood samples of 77 cases (n=19 myelodysplastic syndrome, n=17 acute lymphoblastic leukemia, n=9 chronic myeloid leukemia, n=32 acute myeloid leukemia) with hematological malignancies during the periods of initial diagnosis, treatment, and/or follow-up. RESULTS: Both numerical and structural abnormalities were detected by HTFA. We observed aberrations in 88% of our acute lymphoblastic leukemia patients, 25% of acute myeloid leukemia patients, and 31% of myelodysplastic syndrome patients. In chronic myeloid leukemia cases, aberration was not detected by HTFA. CONCLUSION: Our results showed that HTFA, combined with other methods, will gradually take a place in the routine diagnosis of hematologic malignancies. CONFLICT OF INTEREST: None declared.

A case of del(13)(q14.2)(q31.3) associated with hypothyroidism, hypertriglyceridemia, hypercholesterolemia and total ophthalmoplegia.

13q deletion syndrome is caused by the absence of a portion of the long arm of chromosome 13. This syndrome is a rare condition characterized by a wide range of clinical findings. Phenotype varies with the location and size of the deletion. We report a female dizygotic twin with a proximal deletion of 13q and failure to thrive, hypotonia, and multiple anomalies included pytosis and total ophthalmology at right side, strabismus at left, bilateral iris heterochromia and telecantus. She had a broad nasal bridge with flat philtrum, micrognathia and antevert ear lobes. Her umbilicus had vanished. Her left coxa was dislocated and left toes were overlapped. She was also found to have hypertriglyceridemia, hypercholesterolemia, and hypothyroidism. Chromosome analysis showed a proximal deletion of chromosome 13 [karyotype 46,XX,del(13) (q14.2q31.3)] which was confirmed by high-resolution microarray based comparative genomic hybridization. The described patient is unique among similar rare cases with different deletion breakpoints. It is the first case of 13q14.2q31.3 deletion where the breakpoints are clearly defined, indicating the importance of detailed clinical description and high-resolution genomic analysis for characterization of rare genetic syndromes.

The frequency of MEFV gene mutations in Behcet's disease and their relation with clinical findings.

Investigation of the relation between MEFV gene mutations and clinical findings of Behçet's disease. Genetic features of 100 patients with Behçet's disease (BD) and 100 healthy controls were analyzed. None of the individuals had a family history of FMF in the patient and control group, and none of the individuals in the control group had a family history of BD. MEFV gene analysis was performed in all the patients with BD and healthy controls; twelve different regions were scanned. In the BD group, mutations were detected in more than one region in 27 patients (27%). Twenty-five patients had heterozygous and two patients had compound heterozygous mutations (M680I-V726A and M694 V-A744S). The most frequent mutation was M694 V with an allelic frequency of 5%. The allelic frequencies of E148Q, M680I (G/C), and V726A were 3, 2, and 2%, respectively. The allelic frequencies of P369S, A744S, and K695R were 1, 1, and 0.5%. MEFV gene analysis revealed mutations in 27 (27%) of the individuals in the control group; the allelic frequency was 14%. The most frequent mutation was E148Q that was detected in 16 individuals. One individual was compound heterozygote (E148Q-M694 V). The allelic frequencies of E148Q, M694 V, V726A, and M680I were 8, 3, 1.5, and 0.5%, respectively. The allelic frequencies of K695R and P369S were 0.5 and 0.5%, respectively. The allelic frequency was similar in the two groups. There was not a significant relation between the mutations in the BD group and clinical findings.

Microsurgical anatomy of membranous layers of the pituitary gland and the expression of extracellular matrix collagenous proteins.

BACKGROUND: There are several reports about the microanatomical and histological features of sellar and parasellar membranous structures and clinical studies about MMP proteinase as a predictive factor. However, studies on collagen contents of sellar and parasellar membranous structures are limited. We demonstrated the membranous structures surrounding the pituitary gland and defined extracellular matrix (ECM) collagenous proteins, collagen I-IV expression patterns of sellar and parasellar connective tissues. METHODS: The study was carried out on ten fresh postmortem human bodies at the Forensic Medicine Institution. Cavernous sinuses were resected with sellar structures and were stored at -80°C liquid nitrogen tanks. Medial wall of the cavernous sinus, pituitary capsule and pituitary tissue samples were obtained for RT-PCR. Opposite side specimens were used for histological and immune staining studies. Collagens I-IV were studied by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) methods. FINDINGS: The pituitary capsule and medial wall were identified as two different structures. The fibrous membrane, as the third membrane, was identified as staying whole in eight of ten specimens. Increased type IV collagen was determined in the pituitary gland, medial wall and pituitary capsule, respectively, in both RT-PCR and immunhistochemical studies. Immunhistochemical studies revealed that collagen I was strongly expressed in both the medial wall and pituitary gland. CONCLUSION: Increased type IV collagen was detected especially in pituitary tissue, the medial wall and the pituitary capsule by immune staining and RT-PCR. Type IV collagen was considered to be an important factor in the progression of adenoma and invasion.

ITF2357 interferes with apoptosis and inflammatory pathways in the HL-60 model: a gene expression study.

BACKGROUND: Cytotoxic and pro-apoptotic effects exerted by the histone deacetylase inhibitor ITF2357 have been reported in acute myeloid leukemia HL-60 cells. In the current study, its mechanism of action was investigated at the molecular level. MATERIALS AND METHODS: Cell proliferation was evaluated by methyl thiazol tetrazolium bromide reduction; apoptosis by annexin V, mitochondrial transmembrane potential by tetramethylrhodamine ethyl ester. Functional experiments and gene expression evaluations were performed by flow cytometry, microarray, and quantitative polymerase chain reaction. RESULTS: Significant cell growth inhibition and increased apoptosis were observed. ITF2357 reduced protein levels of BCL-2, MCL-1, and BCL-X, and increased levels of BAK. Exposure to ITF2357 did not abrogate NF-κB DNA binding. After microarray analysis, interleukin-10, interleukin-6, epidermal growth factor, peroxisome proliferator-activated receptor (PPAR), transforming growth factor ß, P38 mitogen-activated protein kinase, aryl hydrocarbon receptor, xenobiotic metabolism, PPAR/retinoic acid receptor, NF-κB, apoptosis, lipopolysaccharide/interleukin-1, G-protein receptor, T-cell receptor, and platelet-derived growth factor were the de-regulated pathways. CONCLUSION: This study shows that ITF2357 influences both proliferation and inflammatory pathways in HL-60 cells; this observation could have possible applications in clinical practice.

Unbalanced 3;22 translocation with 22q11 and 3p deletion syndrome.

This report describes a 25-day-old Turkish boy with unbalanced 3;22 translocation that includes the 22q11.2 deletion and 3p25 deletion syndrome. The karyotype was 45, XY,der(3)t(3;22)(p25;q11),-22. Although no immunological dysfunction could be demonstrated, the boy presented some manifestations of DiGeorge anomaly (DGA), which has been associated with monosomy for the same region of chromosome 22, velocardiofacial syndrome (VCFS), and the 3p deletion syndrome. Clinical features include short stature, hypertelorism, low set ears, cleft lip with cleft palate, short neck, truncus arteriosus, micropenis, clubfoot, over riding toes on right foot, four digits on left foot and growth delay. In addition he had feeding difficulties, respiratory infections, and developmental delay. Fluorescence in situ hybridization (FISH) studies confirmed loss of the proximal DiGeorge chromosomal region (DGCR). Array CGH analysis showed the deletion sites on chromosomes 3 and 22. This report documents a rare chromosomal aberration that causes the 22q11 and 3p deletion syndrome simultaneously.