Mitochondrial haplogroup analysis in colorectal cancer: Identification of a high-risk population

Introduction: Colorectal cancer is the third most common type of non-skin cancer in men (after prostate and Lung cancer) and women (after breast and Lung cancer). The mitochondrion conventionally is often thought to be an organelle specific to energy metabolism. It is in fact multifunctional and has been implicated in many diseases, including cancer. Alterations in the non-coding displacement loop of mitochondrial DNA are present in many types of cancer. In another word this loop has been shown to be a mutation "hot spot" in human cancers. Material and methods: To assess the relationship between mitochondrial DNA haplogroups and colorectal cancer, we sequenced the mitochondrial DNA hypervariable segment I in a study population that comprised 95 cases (55 male, 40 female) and 100 unrelated healthy individuals as a control groups. Haplotypes were assigned according to the West Eurasian mtDNA genealogy. Results: We found that haplogroup K is more frequent in colorectal patients than healthy individuals. That means haplogroup K is significantly more abundant in colorectal cancer patients (P=0.001). Conclusions: In this study we found a significant association of haplogroup K with colorectal cancer in Iranian patients so our finding suggests that mitochondrial genetic background plays a role in modifying an individual's risk for colorectal cancer. Copyright © 2008 Termedia & Banach.Special Medical Center, Tehran, Ira

PTEN gene mutations in patients with macrocephaly and classic autism: A systematic review

Background: Autism Spectrum Disorder (ASD) is a neurological disorder characterized by massive damage in various fields of development. Impaired social interaction and communication skills, unusual behavior or interests, and repetitive activities are considerably disabling in these patients. There are several challenges in diagnosis of ASD patients such as co-existing epilepsy, difference in clinician attitudes and possibly multifactorial etiology of autistic behavior among children and adults. Research in recent years has emphasized a possible connection between mutations in PTEN and macrocephaly (head circumference > 97th centile). Methods: Articles in English Language were searched from international databases including Medline (PubMed), Google Scholar, Scopus, and CINHAL from January 1998 to January 2016. Results: The results showed that among 2940 patients with behavioral disorders, 2755 individuals: had ASD, and 35 cases with macrocephaly had mutations in PTEN. About 77 of the articles (7/9) analyzed mutations in PTEN in patients with head circumference more than 2SD away from the mean, but did not check mutations in this gene in other ASD patients without macrocephaly. To the best of our knowledge, this study is the first systematic review on human PTEN mutations and classical autistic behavior. Conclusion: We conclude that the presence of macrocephaly may not be sufficient to examine the PTEN mutation in this group; however, surveying this gene in all cases of macrocephaly seems to be necessary. © Iran University of Medical Sciences

The importance of BRCA1 and BRCA2 genes mutations in breast cancer development

Many factors including genetic, environmental, and acquired are involved in breast cancer development across various societies. Among all of these factors in families with a history of breast cancer throughout several generations, genetics, like predisposing genes to develop this disease, should be considered more. Early detection of mutation carriers in these genes, in turn, can play an important role in its prevention. Because this disease has a high prevalence in half of the global population, female screening of reported mutations in predisposing genes, which have been seen in breast cancer patients, seems necessary. In this review, a number of mutations in two predisposing genes (BRCA1 and BRCA2) that occurred in patients with a family history was investigated. We studied published articles about mutations in genes predisposed to breast cancer between 2000 and 2015. We then summarized and classified reported mutations in these two genes to recommend some exons which have a high potential to mutate. According to previous studies, exons have been reported as most mutated exons presented in this article. Considering the large size and high cost of screening all exons in these two genes in patients with a family history, especially in developing countries, the results of this review article can be beneficial and helpful in the selection of exon to screen for patients with this disease

Therapeutic impacts of microRNAs in breast cancer by their roles in regulating processes involved in this disease

Breast cancer is the most common cancer in women around the world. So far, many attempts have been made to treat this disease, but few effective treatments have been discovered. In this work, we reviewed the related articles in the limited period of time, 2000�2016, through search in PubMed, Scopus database, Google Scholar, and psychology and psychiatry literature (PsycINFO). We selected the articles about the correlation of microRNAs (miRNAs) and breast cancer in the insight into therapeutic applicability from mentioned genetics research databases. The miRNAs as an effective therapy for breast cancer was at the center of our attention. Hormone therapy and chemotherapy are two major methods that are being used frequently in breast cancer treatment. In the search for an effective therapy for breast cancer, miRNAs suggest a promising method of treatment. miRNAs are small, noncoding RNAs that can turn genes on or off and can have critical roles in cancer treatment; therefore, in the near future, usage of these biological molecules in breast cancer treatment can be considered a weapon against most common cancer-related concerns in women. Here, we discuss miRNAs and their roles in various aspects of breast cancer treatment to help find an alternative and effective way to treat or even cure this preventable disease. © 2017 Journal of Research in Medical Sciences

Analysis of mitochondrial ND1 gene in human colorectal cancer

BACKGROUND: Colorectal cancer as a mortal disease affected both sexes of all ethnic and racial human groups. Former studies have indicated some mutations in the mitochondrial DNA (mtDNA) in different human cancers. Complex I NADH has the most subunits encoded by mtDNA. For a better understanding of the mtDNA abnormality in colorectal cancer some genes of this complex is screened for existence of mutations. METHODS: One of the main regions of the mtDNA encoding protein was screened by PCR-RFLP followed by DNA sequencing. The obtained sequences were aligned with the revised Cambridge Reference Sequence (rCRS). Each alteration recorded as single nucleotide polymorphisms (SNPs), deletions or insertions. RESULTS: Eight mutations were found in 15 samples out of 30 studied populations and no mutation detected in other 15 samples. Among these 15 mutated samples, 7 different mutations were found in 7 patients, that means one mutation per patient and the 8th mutation (T4216C) was common in the rest of 8 samples; in other words T4216C mutation in 27 of tested samples was identified (8 patients out of 30 patients). The existence of T4216C mutation was found to be significantly different (p 0.05) between tumoral patient's tissue and adjacent normal tissue. CONCLUSIONS: Results showed that a high frequency of somatic alterations of mtDNA occurs during the carcinogenesis and/or the progression of colorectal cancer. Based on the mtDNA mutation pattern observed in this study and other previously studies it is believed that looking for somatic mutations in mtDNA would be one of the diagnostic values in early detection of cancer

The association of CNTNAP2 rs2710102 and ENGRAILED-2 rs1861972 genes polymorphism and autism in Iranian population

Autism spectrum disorder (ASD) is a highly heritable neurodevelopment disease characterized by impaired social interactions, communication deficits, restricted interests, stereotyped and repetitive behaviors, which results from the interaction between genetic vulnerability and environmental factors. Our study was aimed to explore the association between CNTNAP2 gene polymorphism (rs2710102 C/T) and ENGRAILED-2 (EN2) (rs1861972 A/G) with the risk of autism in the Iranian population. A total of 67 autism cases and 100 controls were recruited. Single nucleotide polymorphism (SNP) rs2710102 C/T was genotyped by utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and SNP rs1861972 A/G was genotyped by using Tetra-primer ARMS-PCR. The results of this study showed that there is no significant association between rs2710102 CNTNAP2 gene polymorphism and autism, but there is a significant association between rs1861972 EN2 gene polymorphism and autism in the studied population. Consequently, our data provide evidence that the EN2 gene may be implicated in the predisposition to autism in the Iranian population. © 202

Does PTEN gene mutation play any role in Li-Fraumeni syndrome?

Background: Li-Fraumeni syndrome (LFS) is one of the most serious hereditary cancer syndromes with a high risk of malignancy in childhood. This syndrome is an autosomal dominant cancer predisposing syndrome due to a germline mutation in the TP53 tumor suppressor gene. Methods: In this study, a representative family case of Li-Fraumeni syndrome is described. The proband of this family was a 43-year-old male who had osteosarcoma of the mandible and a positive family history of cancer. His mother died at the age of 29 of brain cancer; his sister died at the age of 18 of breast cancer; his brother died at the age of 36 of liver cancer; and another sister of his died at the age of 16 of leukemia. Complete sequence analysis of the TP53 and PTEN genes was performed in this family. We used standard diagnostic tools such as sequencing and multiplex ligation-dependent probe amplification (MLPA) to analyze these two genes in this family. The exons and flanking exon-intron junctions of the TP53 and PTEN genes were sequenced. Results: We detected a germline mutation in the TP53 gene in this family that was previously reported as somatic mutation in LFS in the catalogue of somatic mutations in cancer (COSMIC). In addition, according to the International Agency for Research of Cancer (IARC) database, a 19-year-old male patient with sarcoma was recently reported to have this germline mutation. We also found two new IVS variations in the PTEN gene, one of which can be a suggestive evidence of an effect on the splicing of PTEN. Conclusion: Genomic modifications for tumor risk and genotype-phenotype correlations in LFS are still to be identified. We believe every new finding in this area can provide new insights into the pathogenesis and progression of Li-Fraumeni syndrome

The causative variants of amyloidosis in the autism

Purpose: Autism spectrum disorders (ASD) consist of a group of neurodevelopmental disorders that include autistic behavior, Asperger�s syndrome and pervasive developmental disabilities. According to the increasing observations that patients with mitochondrial disorders have symptoms associated with ASD, we have aimed to analyze the role of mitochondrial DNA (mtDNA) variation in autistic patients. Material and methods: We selected children with autistic behaviors (15�60 CARS Score). The mitochondrial DNA extraction process was done by GeNet Bio DNA extraction kit. The regions of interest were amplified using independent PCR runs. After purification of PCR products, both strands were sequenced by Big Dye Termination system in a directly determined automated sequencing on an ABI 3700 capillary sequencer machine using both primers. All sequencing results were analyzed using bioinformatics� tools sequencher software 5. Results: In this study, 31 samples were examined, which 15 unique variants were detected in genes related to COXI-III. The most frequent variant (30.76) were related to COX1 with amino acid change A � A. The only significant pathogenic variant was C8264G, except for C8264G, all variants seemed to be homoplasmic substitution. Conclusion: In our study, among the variations we found, one variant what probably had an interesting association with possible amyloidosis, had been reported in patient with autism previously. It is hoped that with finding more definable genetic and biological markers, the autistic children diagnosis and treatment will be more effective. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group