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Deletion 9p syndrome is a rare chromosomal abnormality with a wide spectrum of manifestations such as craniofacial dysmorphism, congenital anomalies, and psychomotor delay. We report a case of a seven-year-old girl with simultaneous 9p24.3 deletion and 8p23.3 duplication detected using multiplex ligation-dependent probe amplification (MLPA). Chromosomal and cytogenetic analyses using MLPA are effective in assessing genetic abnormalities in patients with developmental delay and mental retardation. We found breakpoints at 9p24.3 and duplication in the 8p23.3 region, leading to a wide variety of manifestations including speech delay, upslanting palpebral fissures, hypertelorism, epicanthal fold, high arched eyebrows, flat nasal bridge, thin upper lip, and cleft palate. Simultaneous detection of 9p24.3 deletion and 8p23.3 duplication has been rarely reported. Clinical phenotypes of our patient resembled the features of Nicolaides-Baraitser syndrome, which might have been primarily caused by the haploinsufficiency of SMARCA2 (SWI/SNF-related, matrix associated, actin-dependent regulator of chromatin, subfamily A, member 2) gene located at 9p24.3. [ABSTRACT FROM AUTHOR]

Introduction. Vici syndrome (also known as immunodeficiency with cleft lip/palate, cataract, and hypopigmentation and absent corpus callosum) is considered as a progressive neurodevelopmental multisystem disorder. Till date, only 80 cases, including our patient, with this syndrome have been reported.This syndrome is characterized by agenesis of the corpus callosum, hypopigmentation of the eyes and hair, cataract, cardiomyopathy, combined immunodeficiency, hearing loss, seizures, and additional multisystem involvements which have been reported as case reports in the past. Clinical Manifestation. A 5-year-old girl, who is a product of consanguineous marriage, was referred to our center with developmental delay, optic atrophy, blindness, spasticity, seizure, movement disability, and spasticity. Her magnetic resonance imaging (MRI) test showed agenesis of the corpus callosum and her metabolic test reported normal. Materials and Methods. In our laboratory, blood sample was obtained from the patient. DNA was extracted from lymphocytes, and whole exome sequencing (WES) using next generation Illumina sequencing was performed. Result. A novel (private), homozygous, nonsynonymous mutation c.A3206G (p.Y1069C Het) in EPG5 gene was detected; in continuum, testing for this specific variant in her parents was carried out. DNA sequencing of the PCR-amplified product of the EPG5 exon 17 showed that her parents were heterozygote for this variant. These mutations have not been reported before and therefore classified as variation of unknown significance (VUS). Mutation in this gene is shown to cause autosomal recessive Vici syndrome. Conclusion. Since clinical features of Vici syndrome has overlap, its diagnosis is differential and developmental delay occurs in 98% of reported cases. Vici syndrome can be considered as one of the main causes of developmental delay, and this syndrome can be introduced as a novel group of inherited neurometabolic conditions and congenital disorders. [ABSTRACT FROM AUTHOR]

Background: Cancer/testis antigens are a unique class of tumor antigens with normal expressions restricted to the testis and various cancers, but not in adult somatic tissues. Sperm-associated antigen 9 (SPAG9) has been introduced as a new member of Cancer Testis Antigens family involved in c-Jun-NH2-kinase signaling module. The objective of this research was to investigate the potential of SPAG9 as a diagnostic and prognostic biomarker in breast cancer. We further aimed to find any significant association between SPAG9 expression and clinicopathologic features of the cancer. Methods: In this retrospective study, 35 breast cancer tissues and 35 adjacent non-cancerous tissues were collected and examined using RT-PCR to explore SPAG9 mRNA expression. Statistical analysis was done utilizing SPSS 22.0 software. Results: Unexpectedly, we detected SPAG9 expression in 54% of adjacent noncancerous tissues. Moreover, SPAG9 mRNA was expressed in 57% of cancerous tissues. Statistical analysis showed a significant association between SPAG9 expression and tumor size, lymph node metastasis, and cancer stage. Conclusion: The association between the gene expression and tumor size, lymph, node and metastasis, and cancer stage suggests that SPAG9 can potentially be considered as a prognostic biomarker in breast cancer. However, it may not be a candidate diagnostic biomarker. [ABSTRACT FROM AUTHOR]

Abstract Molecular alterations that occur in cancer have the potential to be considered as either cancer biomarkers or targeted therapies or even both. In the presented study, we aimed to elucidate the gene regulatory network of metastatic colorectal cancer using data acquired from microarrays to reach the most common DEGs in colorectal cancer metastasis and find their possible regulatory mechanism by DETFs and DEmiRs. In this regards, seven microarray datasets were employed to assess the most important DEGs, DETFs and DEmiRs in colorectal cancer metastasis. Afterward, GRN based on DETFs and DEmiRs were constructed. Also ARACNE algorithm was used to construct an accurate GRN. GRN was analyzed structurally and then, two DETFs (LEF1 and ETV4) and a less-well known DEG (FABP6) by real time qRT-PCR in 50 patients with colorectal cancer were quantified. The constructed GRN highlighted the importance of some DETFs and DEmiRs in colorectal cancer metastasis. Interestingly the gene expression analysis by qRT-PCR on three candidate genes (LEF1 , ETV4 and FABP6) indicated that the three genes were co-expressed in tumor samples, and were significantly associated with metastasis in colorectal cancer. Therefore, our experimental results proved a part of our comprehensive data analysis and system biology results. In summary, according to our empirical study we found the importance of three candidate genes as the potent prognostic factors in colorectal cancer metastasis. Also our study in a holistic insight on gene regulatory mechanism revealed the importance of some gene regulatory factors (DETFs and DEmiRs) and their potential as prognostic factors and/or targets in molecular targeted therapies in colorectal cancer. Highlights • Identification of the common DEGs, the most important DETFs and DEmiRs in metastatic colorectal cancer. • Construction of an accurate GRN for metastatic colorectal cancer and structural analysis of the depicted GRN. • Highlighting the importance of the cell membrane and the extracellular matrix as the main cellular components in colorectal cancer metastasis. • Identification of Wnt and Hippo signaling pathways which complicated with the main DETFs in metastatic colorectal cancer. • Evaluation of the selected three candidate genes as three co-regulated prognostic markers in colorectal cancer metastasis. [ABSTRACT FROM AUTHOR]

BACKGROUND Colorectal cancer (CRC) is one of the most common cancers among men and women worldwide. Cancer metastasis is the main cause of death in patients with cancer. NEBL (nebulette, Gene ID: 10529) protein interacts with thin filaments in the cell and may functionally destabilize focal adhesion composition. There are some studies on NEBL gene expression alteration in cancer. In the presented study we aimed to analyze NEBL gene expression in patients with colorectal cancer to explore possible association of this gene with clinicopathological features in CRC. METHODS Sixty-seven fresh samples of colorectal tumors and adjacent normal tissues were collected from Iranian patients with CRC. Real time polymerase chain reaction was performed to measure the level of NEBL gene expression and its association with clinico-pathological features. RESULTS A significant overexpression with 3 fold increse was seen in NEBL mRNA level in tumoral tissues compared with the adjacent normal tissues. In addition there was a significant association between NEBL gene expression with lymph node metastasis in patients with CRC. CONCLUSION The overexpression of NEBL has the capacity to be considred as a prognostic biomarker in patients with CRC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fibulin-4 (FBLN-4) is an extracellular glycoprotein that is upregulated in some cancer and is khown as prognostic marker in ovarian and cervical cancer. Breast cancer resistance protein (BCRP) is an ATP-binding cassette transporter that facilitates the efflux of various anticancer drugs from the cell and cause MDR phenotype in breast tumors. Many studies are available that indicat overexpression of BCRP gene in breast cancer. OBJECTIVE: In the present study we aimed to analyze the expression level of FBLN-4 and BCRP in Iranian breast cancer patients. METHODS:We collected 40 samples of breast cancer and normal tissue from Tehran Khatam-al-Anbia hospital. To analyze the gene expression by using Real Time RT-PCR FBLN-4 and BCRP gene expression level were measured and then the association of gene expression with breast cancer were determined. RESULTS: Surprisingly the expression level of FBLN-4 and BCRP genes were downregulated in tumor tissues compared to adjacent normal tissues. Comparison of the gene expression and clinico-pathology reports indicate FBLN-4 gene expression was associated with breast cancer histological grade. We found no correlation between the expressions of BCRP gene with any clinico-pathological characters. CONCLUSION: Interestingly and in contrast with our expectation, we found that the expression level of FBLN-4 and BCRP were downregulated in tumor compared to adjacent normal tissues. FBLN-4 was associated with grade histology and therefore can be considered as a potential prognostic biomarker. [ABSTRACT FROM AUTHOR]

Background & objectives: Lipoid proteinosis (LP) is an autosomal recessive disease. Clinical characteristics of this disease are hoarse voice, scarring of the skin, brain calcifications, and eyelid papules (moniliform blepharosis). Mutations in the ECM1 gene on 1q21.2 are responsible for this disease. This study was conducted to investigate the mutation spectrum of ECM1 gene in nine Iranian families having at least one LP patient diagnosed clinically. Methods: The entire ECM1 gene was screened using PCR and direct sequencing in nine Iranian families with 12 suspected LP patients who were referred to the clinic, along with their parents and siblings. Thirty healthy individuals were included as controls. Results: In only one patient a homozygous G>A transition at nucleotide c.806 in exon 7 was detected. A G>A substitution at nucleotide 1243 in exon 8 that changes glycine (GGT) to serine (AGT) was observed in most of our patients. Furthermore, in one patient there was a change in the sequence of intron 8, the A>T transition in nucleotide 4307. In addition, in two cases (one patient and one healthy mother with affected child) there was a C (4249) deletion in intron 8. Interpretation & conclusions: Our results indicate that although mutation in ECM1gene is responsible for lipoid proteinosis, it is likely that this is not the only gene causing this disease and probably other genes may be involved in the pathogenesis of the LP disease. [ABSTRACT FROM AUTHOR]

Background & objectives: Fanconi anaemia (FA) is a syndrome with a predisposition to bone marrow failure, congenital anomalies and malignancies. It is characterized by cellular hypersensitivity to crosslinking agents such as mitomycin C (MMC). In the present study, a new approach was selected to investigate FANCA (Fanconi anaemia complementation group A) gene in patients clinically diagnosed with cellular hypersensitivity to DNA cross-linking agent MMC. Methods: Chromosomal breakage analysis was performed to prove the diagnosis of Fanconi anaemia in 318 families. Of these, 70 families had a positive result. Forty families agreed to molecular genetic testing. In total, there were 27 patients with unknown complementary types. Genomic DNA was extracted and total RNA was isolated from fresh whole blood of the patients. The first-strand cDNA was synthesized and the cDNA of each patient was then tested with 21 pairs of overlapping primers. High resolution melting curve analysis was used to screen FANCA, and LinReg software version 1.7 was utilized for analysis of expression. Results: In total, six sequence alterations were identified, which included two stop codons, two framesshift mutations, one large deletion and one amino acid exchange. FANCA expression was downregulated in patients who had sequence alterations. Interpretation & conclusions: The results of the present study show that high resolution melting (HRM) curve analysis may be useful in the detection of sequence alteration. It is simpler and more costeffective than the multiplex ligation-dependent probe amplification (MLPA) procedure. [ABSTRACT FROM AUTHOR]

Background: Huntington disease (HD) is a dominantly inherited, neurodegenerative disease characterized by choreiform movement disturbances and dementia. The onset age of this disease is varied but usually is between the ages 40-50. Huntington's disease is caused by a triplet-repeat expansion in the IT15 gene (also known as huntingtin or HD) which is located on chromosome 4p3.1. Since many clinical picture of HD are indistinguishable from other distinct genetic disorders molecular test such as PCR is the only way to confirm the disease. The aim of this study was to introduce a new and fast technique for the diagnosis of Huntington disease. Materials and Methods: Blood specimens were collected from individuals suspected for Huntington disease and also people with no symptoms and family history of this disease. DNAs were extracted according to standard protocol. Using conventional PCR, patient positive for Huntington disease were diagnosed. Then employing real time PCR on the basis of difference between melting temperature (Tm) a new and fast diagnostic method was introduced. Results: Among 29 patients suspected to be HD only 8 HD patients were confirmed using PCR and real time PCR. The numbers of CAG repeat were between 42-50 and melting temperatures were between 89-92. Conclusion: The concept of using melting temperature in real time PCR protocol presented in here could be employed for the rapid diagnosis of the diseases caused by the increased in triple repeat sequences. It is fast, robust and has the potential use for the prenatal diagnosis. [ABSTRACT FROM AUTHOR]

A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR) assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of somatic chromosomal abnormalities in infertile male individuals has been reported to vary in different literatures. The aim of this study was to investigate the frequency of chromosomal aberrations among infertile men referred to the Cytogenetic Laboratory of Iran Blood Transfusion Organization Research Centre (IBTO).Materials and Methods: Chromosomal analysis was performed on phytohemagglutinin (PHA)-stimulated peripheral lymphocyte cultures of 1052 infertile men using standard cytogenetic methods. The study took place during 1997 to 2007. Results: Total chromosome alterations were revealed in 161 (15.30%) infertile men. The most prevalent chromosomal abnormality in the infertile men was 47, XXY, that was seen in 94 (58.38%) men while one of them had a mosaic karyotype: mos 47, XX[54]/47,XXY[18]/46,XY[9]. In 37 (22.98%) cases, structural aberrations were detected. There were 30 (18.63%) cases of sex reversal. Conclusion: Cytogenetic studies of these patients showed increased chromosomal abnormalities in infertile men in comparison with that of the normal population, justifying the need for cytogenetic analysis of men with idiopathic infertility. [ABSTRACT FROM AUTHOR]

The nucleotide (nt) variations in the promoter region of the γ-globin genes, HS-111 and 3′HS1 regions, were studied in Iranian patients with β-thalassemia intermedia (β-TI), β-thalassemia major (β-TM) and healthy individuals. Of the five nt variations at the 5′ end of the Aγ-globin gene, −369 (C>G), −611 (−T) and −603/604 (GA>AG) were found in all samples, whereas −588 (A>G) and −AAGC at −222 to −225 were found at different frequencies in the studied groups. Therefore, the −369, −611 and −603/604 variations were considered common mutations in this population, and the difference with respect to the −AAGC deletion was not significant. However, the A allele of the −588 variation and [+] allele of the XmnI polymorphism were more frequent in β-TI patients, especially those who had the IVS-II-1(G>A)/IVS-II-1(G>A) genotype. The + allele of XmnI also had complete correlation with the A allele of −588 variation. The HS-111 (−21 A) variation also showed association with β-TI patients who had high levels of Hb F. Bearing in mind that the −588 variation lies within the postulated adult-specific silencer region and that the majority of β-TI patients had allele A, then it can be envisaged that this allele could have a role in altering the repressor function at this region. Therefore, the A allele of −588, [+] allele of XmnI and HS-111 (−21 A) variation are useful genetic markers to differentiate between β-TM and β-TI patients. However, these nt changes alone may not be the only elements raising the level of Hb F, other regulatory and modifying factors also play a role in Hb F production. [ABSTRACT FROM AUTHOR]

Background: Upregulation of multidrug resistance-associated protein (MRP1) gene has been detected in many in vitro systems and could be the basis of the drug resistance phenotype in vivo. Increase in gene dosage and overexpression are two major mechanisms for increasing MRP1 expression level. In many drug resistant cell lines, MRP1 gene amplification has been detected. However, it is not yet known whether gene amplification plays a role in inducing the multidrug resistance phenotype clinically. Methods: To establish whether MRP1 gene copy number is a common feature of the upregulation of MRP1 expression in cancer patients, we studied the MRP1 gene copy number in leukemia patients by fluorescent in situ hybridization (FISH) and real-time PCR. This involved determination of the MRP1 gene copy number and mRNA level in the peripheral blood of 52 adult leukemic patients and ten healthy volunteers. The leukemic CCRF-CEM cell line (drug sensitive) and its drug-resistant subline CCRF-E1000, which has MRP1 overexpression, were used as controls. Results: The MRP1 gene copy number in CCRF-CEM was normal but increased significantly in CCRF-E1000 cell line. However, in the presence or absence of MRP1 overexpression, increase in gene dosage was not detected in patients. Conclusions: Our data suggest that the increase in MRP1 gene dosage observed in resistant cell lines is not responsible for the upregulation of MRP1 expression in leukemic patients. [Copyright &y& Elsevier]

Background: Pathogenic mutations in TRAPPC9 are associated with autosomal recessive Intellectual Disability (ID), a major public health issue that affects about 1–3% of children worldwide. Method: Clinical evaluation, magnetic resonance imaging, peripheral blood karyotype, Multiplex ligation‐dependent probe amplification (MLPA), array CGH, and whole‐exome sequencing were used to characterize etiology in three patients from two unrelated consanguineous families of Iranian descent with intellectual disability. Results: Whole‐exome sequencing showed two novel homozygous nonsense mutations (c.937C>T) in exon 3 and (c.3103C>T) in exon 19 of TRAPPC9 (NM_031466.7) in two unrelated consanguineous families. Conclusion: The two novel variants found in TRAPPC9 caused truncated protein and clinical manifestations such as ID, developmental delay, microcephaly, and brain abnormalities in three patients. [ABSTRACT FROM AUTHOR]

Background: Sex determining region Y box transcription factor 2 (SOX2) mutations lead to bilateral anophthalmia with autosomal dominant human inheritance. SOX2 mutations could result in severe ocular phenotypes usually associated with variable systemic defects. Most patients described with SOX2 anophthalmia syndrome possessed de novo mutations in this gene. Case Presentation: In this case report, we describe 2 brothers with mental retardation and bilateral anophthalmia caused due to SOX2 germline mosaicism in unaffected parents. Next-generation DNA sequencing was carried out to determine the family's possible cause of genetic mutation. Sanger sequencing was performed on the patients and their parents. Prenatal diagnosis was done in both pregnancies of the older brother's wife via chorionic villus sampling. A novel heterozygous pathogenic frameshift deletion variant (exon1:c.58_80del:p.G20fs) was identified in the SOX2 gene, which was confirmed by Sanger sequencing in both affected brothers and did not exist in healthy parents, indicating germline mosaicism. Conclusion: Most SOX2 mutations known look to arise de novo in probands and are diagnosed through anophthalmia or microphthalmia. Prenatal diagnosis should be offered to healthy parents with a child with SOX2 mutation every pregnancy. [ABSTRACT FROM AUTHOR]

Aim/Background: Colorectal carcinoma cancer is one of the main types of cancer with high death rate of patients, according to their non-healthy lifestyle. In this research, we evaluated inhibitory of white tea clone 100 extract on colorectal cancer cell line HCT-116, and its effectiveness in expression level of three tumor suppressor genes. Materials and Methods: Total polyphenolic content in all samples were measured using the Folin–Ciocalteu method, and free radical adsorption investigated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the white tea extract inhibitory effect on HCT-116 cells. Results: Among different extraction methods, the white tea aqueous extracts produced the highest amount of polyphenols and DPPH radical scavenging activity (36.67 ± 0.54 mg gallic acid equivalent/g dry weight and 71.74% ± 0.42%, respectively). Cell survival analysis in the MTT assay indicated that aqueous white tea extract could reduce the viability of HCT-116 cells in 8, 16, and 24 h considerably, related to the concentration-dependent manner. The real-time polymerase chain reaction results indicated the significantly increased expression level (P < 0.05) of tumor suppressor genes DCC , TGFBR2 , and P53 in the concentration of 1000 mg/ml at 24 h. Conclusion: White tea aqueous extract because of having hydroxyl group in its structure at optimal concentration in all three times of experimental, could lead to a positive changes effect on gene expression in the tumor suppressor family. Key words: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, HCT-116 cell line, radical scavenging activity, tumor suppressor genes, white tea [ABSTRACT FROM AUTHOR]

A letter to the editor related to a study reporting cretan type of nondeletional hereditary persistence of fatal hemoglobin in an Iranian family is presented.

Purpose: To evaluate the total content of polyphenols and the free radical scavenging activity of three different extracts of three types of tea clone 100 (black, green and white), and their anti-proliferative effects on colorectal cancer. Methods: Five major polyphenols, viz, (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate, were identified using thin layer chromatography (TLC). Catechins were quantified by high performance liquid chromatography (HPLC). Antioxidant activity was measured by DPPH radical scavenging method, while 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) assay was employed for the determination of cell viability of colon cell line HCT-116 after 24 and 48 h. Results: The aqueous methanol (70 %) extract of white tea yielded the highest amount of polyphenols (36.67 ± 0.54 mg GAE/g dry weight). The DPPH radical scavenging activity of white tea was 71.74 ± 0.42 %, and it produced high anti-proliferation activity against colorectal cancer cell line HCT-116 (86.06 ± 0.54 %). Conclusion: White tea extract possesses high DPPH radical scavenging activity, and exerts good antiproliferative effects against colorectal cancer cell line HCT-116, most likely due to its catechin content. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and can be caused by a variety of genetic and acquired/environmental factors. Bax-interacting factor-1 (Bif-1) is an apoptosis inducer gene that interacts with the Bcl2 protein family and triggers apoptosis via direct contact or by changing into the Bax protein conformation using the phosphorylation mechanism. Bif-1 also interacts with Beclin-1, a protein that plays a central role in autophagy through mediation of UVRAG (ultraviolet irradiation resistant-associated gene), a positive regulator of phosphatidylinositol 3-kinase complex 3 (PI3KC3), thereby inducing autophagy in mammalian cells. Considering the dual role of Bif-1 in many tumors of different origins, in this study we assessed Bif-1 gene expression to investigate its potential role as a possible prognostic biomarker in Iranian colorectal cancer patients. Methods: Bif-1 gene expression in tumors and normal adjacent tissues in 50 colorectal cancer patients were quantified using Real-time RT-PCR. Also, the association between Bif-1 gene expression levels with the histopathological characteristics of patients was assessed. Results: The results indicated an overall upregulation of the Bif-1 gene in colorectal tumors compared with normal adjacent tissues (p < 0.0001). Also, Bif-1expression was significantly elevated in stages II and III compared with stage I, and down-regulated in stage IV patients with distant metastasis. A positive association was also observed between lymph node involvement and tumor size ≥ 5 centimeters with Bif-1 overexpression (P < 0.001). Conclusion: In conclusion, up-regulation of the Bif-1 gene could be considered as a possible prognostic candidate in colorectal cancers associated with nodal metastasis and greater tumor size. Further validation of these results are recommended in studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

Epigenetic modifications are known to regulate cell phenotype during cancer progression, including breast cancer. Unlike genetic alterations, changes in the epigenome are reversible, thus potentially reversed by epi-drugs. Breast cancer, the most common cause of cancer death worldwide in women, encompasses multiple histopathological and molecular subtypes. Several lines of evidence demonstrated distortion of the epigenetic landscape in breast cancer. Interestingly, mammary cells isolated from breast cancer patients and cultured ex vivo maintained the tumorigenic phenotype and exhibited aberrant epigenetic modifications. Recent studies indicated that the therapeutic efficiency for breast cancer regimens has increased over time, resulting in reduced mortality. Future medical treatment for breast cancer patients, however, will likely depend upon a better understanding of epigenetic modifications. The present review aims to outline different epigenetic mechanisms including DNA methylation, histone modifications, and ncRNAs with their impact on breast cancer, as well as to discuss studies highlighting the central role of epigenetic mechanisms in breast cancer pathogenesis. We propose new research areas that may facilitate locus-specific epigenome editing as breast cancer therapeutics. [ABSTRACT FROM AUTHOR]

Aim: To explore biomarkers with a tumor stage-dependent expression pattern in patients with colorectal cancer (CRC). Background: The fourth most common cancer in the world is colorectal cancer (CRC). A variation in the gene expression rate is a common change in cancers initiation and the accumulation of these variation changes the behavior of normal cells and turns them into cancer cells. Methods: Real-time RT-PCR was used to investigate the expression patterns of the FOXM1, PYROXD1, hTERT, BMI, PPARA, PIM3 and MCTP1 genes in 54 patients with stage I to IV CRC and their relation with clinicopathological features of CRC were analyzed. Results: FOXM1, hTERT and MCTP1 genes are overexpressed in CRC tumor tissues when compared to normal adjacent tissues in all the stages. Results FOXM1, PYROXD1, hTERT, PM3, BMI1, PPARA and MCTP1 had-stage dependent expression. Investigation of the association between clinicopathological features and expression pattern of the studied genes revealed; a) a significant relationship between FOXM1 gene expression level and tumor stage, tumor size and lymph node involvement, b) a considerable association between alterations in PPARA and PIM3 expression and lymph node involvement, c) a notable correlation between hTERT expression level and the tumor stage and d) a strong correlation between MCTP1 expression and patient's age only. Conclusion: Our study indicates that expression profiles of these genes either individually or together can be applied as potential biomarkers for prognosis of CRC. [ABSTRACT FROM AUTHOR]

Background: Resistance to wide range of structurally and functionally different chemotherapy drugs acts as a major obstacle in the cancer therapy. There are different mechanisms that cause multi drug resistance (MDR) but the most important one is ATP Binding Cassette (ABC) transporters super-family that increases the ability of tumor cells to transport drugs out of the cells by using ATP molecule, over expression of these proteins such as MDR1 and MRP1 is responsible for MDR phenotype in cancerous cells. Materials and Methods: We analyzed the expression level of MDR1/MRP1genes by using Real time RT-PCR in 60 colorectal cancer patients also we investigate their relationship with clinical, Para-clinical characterizes of colorectal cancer patients and their responses to treatment. Results: The expression of the MDR1 gene showed a significant increase in cancerous regions compared to adjacent normal tissue. In addition the expression of MDR1 gene showed association with histological grade of tumors but expression level of MRP1 was not significantly important. Conclusion: Our study once more emphasizes the effects of MDR1 over expression which impact on response to drugs in Iranian colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: l-Gulono-gamma-lactone oxidase (GULO) is a key enzyme for the biosynthesis of ascorbate, which is essential for several cellular functions. In the present study, mRNA expression of GULO gene was evaluated during the early development of Persian sturgeon. First, because there are no comparative studies that have established suitable quantitative real-time PCR reference genes in sturgeons for any physiological conditions, we evaluated six candidate reference genes (ACTB, RPL13, UBQ, RPL6, GAPDH and EF1A) during the early development of Persian sturgeon. The most stable mRNA expression was obtained with RPL6 and ACTB, whereas the least stable was RPL13. After normalization using RPL6, ACTB and RPL6/ACTB combination, the mRNA expression of GULO was highest at the embryonic stage (2days before hatching; P <0.05) and started to decline from hatching of larvae to the rest of the developmental time-points. This suggests that the vitamin C requirements are highest during early life stages, and it is likely that the changes in GULO mRNA expression are associated with changes in GULO enzyme activity. [Copyright &y& Elsevier]

Aim: Efforts to explore biomarkers and biological pathways involved in the disease are needed to improve colorectal cancer (CRC) diagnosis and alternative treatments Background: The fourth common malignancy in the world is colorectal cancer. The over-all burden is predicted to rise by 2030. Methods: In the current study, nine genes were selected. Previously, a panel of genes by Agendia, a classifier of robust gene expression (ColoPrint), was determined to significantly improve the prognostic accuracy of pathologic factors in stage II and III colorectal cancer patients. Five genes, including Ppara, Mctp1, Pyroxd1, Il2r, and Cyfip2, from this panel and four other genes which were not in this panel but were cited abundantly in the literature were selected. Then, expression levels of the selected genes in CRC tissue were compared with levels in adjacent normal tissue. To identify the pathways involved in CRC, gene set enrichment analysis was subsequently performed. Furthermore, to illustrate the relationship between genes in this disease, the cross-shaped co-expression pattern and gene regulatory network were determined using computational methods. Results: This research found that the pairs of genes: {Il2r, Cyfip2}, {Foxm1, Ppara}, {Mctp1, Ctsc} and {Pyroxd1, Cyfip2} are functionally related. Furthermore, two differentially expressed gene pairs {Foxm1, Ppara} and {Il2r, Cyfip2} are involved in the vascular endothelial growth factor receptor signaling pathway and the purine ribonucleoside diphosphate metabolic process, respectively. Conclusion: This research found that the combination of computational analysis and laboratory data provided the opportunity to better characterize the relation between central colorectal cancer genes as well as possible pathways involved in the colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: To make the right treatment decisions about colorectal cancer (CRC) patients reliable predictive and prognostic data are needed. However, in many cases this data is not enough. Some studies suggest that LRIG1 gene (leucine-rich repeats and immunoglobulin-like domains1) has prognostic implications in different kinds of cancers. Methods: One hundred and two patients with colorectal cancer were retrospectively analyzed for LRIG1 expression at both mRNA and protein levels. SYBR Green Real-Time RT-PCR technique was used for mRNA expression analyses and Glyceraldehyde-3-Phosphate Dehydrogenase gene (GAPDH) was considered as a reference gene for data normalization. LRIG1 protein expression was analyzed using Immunohistochemistry. Additionally, appropriate statistic analyses were used to assess the expression of LRIG1 in test and control groups. The prognostic significance of LRIG1 expression was analyzed using the univariate and multivariate analyses. Results: The data revealed that the expression of LRIG1 in both mRNA and protein levels was down regulated in colorectal tumor tissues (P < 0.01) but is not clinically relevant prognostic indicator in CRC. Conclusions: Therefore, it is suggested that LRIG1 expression analyses may not be considered as an important issue when making informed and individualized clinical decisions regarding the management of colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Background: Exposure to benzene would be associated with many diseases including leukemia. Epigenetic alterations seem to be among the main mechanisms involved. Objective: To determine if chronic occupational exposure to low level of benzene would be associated with DNA methylation. Methods: Global DNA methylation and promoter-specific methylation of the two tumor suppressor genes, p14ARF and p15INK4b, were assessed employing methylation-specific PCR using the DNA extracted from 40 petrochemical workers exposed to ambient benzene levels of <1 ppm, and 31 office workers not exposed to benzene or its derivatives. Results: While an increase in global DNA methylation of 5% in p14ARF (p=0.501) and 28% in p15INK4b (p=0.02) genes was observed in the exposed group, no hypermethylation in either of the studied genes was observed in the unexposed group. No significant association was found between the frequency of aberrant methylation and either of age, work experience, and smoking habit in the exposed group. Conclusion: Chronic occupational exposure to lower than the permissible exposure limit of benzene may still result in DNA methylation of tumor suppressor genes that may ultimately lead to development of cancer. [ABSTRACT FROM AUTHOR]

Background: Iran is ethnically, linguistically and religiously diverse. However, little is known about the population genetics of Iranian religious communities. Aim: This study was performed in order to define the different paternal components of the Iranian gene pool. Subjects and methods: Fourteen Y chromosome bi-allelic markers were analysed in 130 male subjects from Assyrian, Armenian and Zoroastrian groups in comparison with 208 male subjects from three Iranian Muslim groups. Results: Among the three Iranian Muslim groups, the Uromian people possessed a particularly close genetic relationship to the Armenian, whereas the Zoroastrian group was different from the Uromian, but had a close genetic relationship to the two other Muslim groups (Kermanian and Shirazian). The genetic results indicate a relationship between Armenian and Assyrian groups in Iran and a clear distinction of the former from the Zoroastrian group. However, Assyrians had elevated frequency (40%) of R**(xR1a) and low frequency (11%) of J. Conclusion: The results of this study may suggest that the Assyrian population either experienced Eurasian gene flow (possibly from Armenia) or that enforced relocations and expulsion of conquered people with different origin led to the integration of descendants with R haplogroup. This could also be due to genetic drift due to small population size and endogamy resulting from religious barriers. [ABSTRACT FROM AUTHOR]

Objective: To study the possible association between high levels of fetal haemoglobin (HbF) in β-thalassemia intermedia patients and HS-111 and 3'HS1 sequence variations. Materials and Methods: In this study, the 3' HS-1 and HS-111 regions of 30 β-thalassaemia intermedia patients (β°/β°) with high levels of HbF, 21 β-thalassemia major patients and 40 normal Iranian individuals were analyzed by single-strand conformation polymorphism (SSCP) and polymerase chain reaction (PCR) sequencing. Results: Two nucleotide variations in 3' HS111 (-21A>G) and 3'HS1 (179C>T) were identified. The most frequent sequence variation was 3' HS111 (-21A) in the intermedia patients and 3'HS111 (-21G) in the major thalassemia patients. In contrast to the 3'HS1 marker, both 3'HS111 A and G variants showed a correlation with each studied group. Conclusion: The HS111 marker in conjunction with other parameters could be used as appropriate genetic markers to discriminate β-thalassemia intermedia patients (β°/β°) with high levels of HbF from β-thalassemia major patients. [ABSTRACT FROM AUTHOR]

• His-GQDs synthesized via pyrolysis green-synthesis route. • His-GQDs were used for cellular imaging of ACHN cell lines as a novel bright green fluorescence probe. • This is the first reported of label-free, selective and non-toxic fluorescence probe for cellular imaging of ACHN cell lines. • Cellular imaging was achieved successfully show that His-GQDs can be easily penetrated into cytoplasm. In this study, bright green-luminescent probe (His-GQDs) were synthesized using a new one-pot "bottom-up" pyrolysis green-synthesis route, without consuming any water and chemical reagent. Citric acid as carbon source and Histidine as amino-functionalized agent, with optimized ratios, were used for fabricating His-GQDs as a novel, label-free, and selective probe. His-GQDs can be then used for cellular imaging of human ACHN cell lines that are composed of graphene sheets with the average size of 2.0 nm. Obtained His-GQDs probe has ultra-small size, low toxicity, chemical stability, biocompatibility, anti-photo bleaching and excellent optical properties with a rather high quantum yield of 62.8%. The detailed structural studies were confirmed by FT-IR, HR-TEM and powdered X-ray diffraction analysis respectively. In this project, the His-GQDs were utilized for cellular imaging of human ACHN cell lines for the first time. This probe indicated the presence desired biocompatibility of His-GQDs in human ACHN cell lines even at high their concentration (1800 µg mL−1) at 24 h post-treatment and their distribution in ACHN cell lines cytoplasm. [ABSTRACT FROM AUTHOR]