• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4509-4513
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• 2013

Chronic hepatitis B virus (HBV) infection has long been the most common cause of hepatocellular carcinoma (HCC). However, some aspects of the pathogenesis of HBV infection and genesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) are still inconclusive. An increasing number of published studies indicate that hepatitis B virus mutations are associated with risk of HCC. These variations include, in particular, mutations in ORF S,C,X gene regions. This mini-review summarizes results of clinical studies and molecular mechanisms on the possible relations of HBV mutations with the development of hepatocellular carcinoma.

• Journal of the Korea Society of Computer and Information
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• v.21 no.9
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• pp.101-106
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• 2016

The epidermal growth factor receptor(EGFR) protein kinase signaling is an important pathway in cancer development and recently reported that EGFR and its kinase domain molecules are mutated in various of cancers including head and neck cancer. Functional deregulation of EGFR due to mutations in coding exons and copy number amplification is the most common event in cancers, especially among receptor tyrosine kinases(TK). We have analyzed Korean oral squamous cell carcinomas (OSCC) cell lines for mutations in EGFRTK. Exons encoding the hot-spot regions in the TK domain of EGFR (exons 17 to 23) were amplified by using polymerase chain reaction(PCR) and sequenced directly. EGFR expression was also analyzed in 8 OSCC cell lines using western blotting. Data analysis of the EGFR exons 17 to 23 coding sequences did not show any mutations in the 8 OSCC cell lines that were analyzed. The absence of mutations indicate that protein overexpression might be responsible for activation rather than mutation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1247-1253
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• 2014

Mutations in the DNMT3A and IDH genes represent the most common genetic alteration after FLT3/NPM1 in acute myeloid leukemia (AML). We here analyzed the frequency and distribution pattern of DNMT3A and IDH mutations and their associations with other molecular markers in normal karyotype AML patients. Fortyfive patients were screened for mutations in DNMT3A (R882), IDH1 (R132) and IDH2 (R140 and R172) genes by direct sequencing. Of the 45 patients screened, DNMT3A and IDH mutations were observed in 6 (13.3%) and 7 (15.4%), respectively. Patients with isolated DNMT3A mutations were seen in 4 cases (9%), isolated IDH mutations in 5 (11.1%), while interestingly, two cases showed both DNMT3A and IDH mutations (4.3%). Nucleotide sequencing of DNMT3A revealed missense mutations (R882H and R882C), while that of IDH revealed R172K, R140Q, R132H and R132S. Both DNMT3A and IDH mutations were observed only in adults, with a higher frequency in males. DNMT3A and IDH mutations were significantly associated with NPM1, while trends towards higher coexistence with FLT3 mutations were observed. This is the first study to evaluate DNMT3A/IDH mutations in Indian patients. Significant associations among the various molecular markers was observed, that highlights cooperation between them and possible roles in improved risk stratification.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4511-4515
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• 2016

Background: K-RAS and N-RAS gene mutations cause resistance to treatment in patients with colorectal cancer. Based on this, awareness of mutation of these genes is considered a clinically important step towards better diagnosis and appropriate treatment. Materials and Methods: Fifty paraffin-embedded blocks of colorectal cancer were obtained from Imam Reza Hospital of Birjand, Iran. Following DNA extraction, the samples were analyzed for common mutations of exons 2, 3 and 4 of KRAS and NRAS genes using real time PCR and pyrosequencing. Results: According to this study, the prevalence of mutations was respectively 28% (14 out of 50) and 2% (1 out of 50) in KRAS and NRAS genes. All the mutations were observed in patients >50 years old. Conclusions: Mutations were found in both KRAS and NRAS genes in colorectal cancers in Iranian patients. Determining the frequency of these mutations in each geographical region may be necessary to benefit from targeted cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5211-5217
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• 2015

Background: We earlier used PCR-dHPLC for mutation analysis of BRCA1 and BRCA2. In this article we report application of targeted resequencing of 30 genes involved in hereditary cancers. Materials and Methods: A total of 91 patient samples were analysed using a panel of 30 genes in the Illumina HiScan SQ system. CLCBio was used for mapping reads to the reference sequences as well as for quality-based variant detection. All the deleterious mutations were then reconfirmed using Sanger sequencing. Kaplan Meier analysis was conducted to assess the effect of deleterious mutations on disease free and overall survival. Results: Seventy four of the 91 samples had been run earlier using the PCR-dHPLC and no deleterious mutations had been detected while 17 samples were tested for the first time. A total of 24 deleterious mutations were detected, 11 in BRCA1, 4 in BRCA2, 5 in p53, one each in RAD50, RAD52, ATM and TP53BP1. Some 19 deleterious mutations were seen in patients who had been tested earlier with PCR-dHPLC [19/74] and 5/17 in the samples tested for the first time, Together with our earlier detected 21 deleterious mutations in BRCA1 and BRCA2, we now had 45 mutations in 44 patients. BRCA1c.68_69delAG;p.Glu23ValfsX16 mutation was the most common, seen in 10/44 patients. Kaplan Meier survival analysis did not show any difference in disease free and overall survival in the patients with and without deleterious mutations. Conclusions: The NGS platform is more sensitive and cost effective in detecting mutations in genes involved in hereditary breast and/or ovarian cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.5019-5022
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• 2014

Recently, mutations in the genes involved in cell cycle control, including CHEK2, are being considered as etiological factors in different kinds of cancers. The CHEK2 protein plays an important role in protecting damaged DNA from entering mitosis. In this study the potential effects of two common mutations $IVS2+1G{\rightarrow}A$ and Ile157Thr of CHEK2 gene in differentiated thyroid carcinoma (DTC) were evaluated. A total of 100 patients admitted to the Research Institute for Nuclear Medicine were diagnosed with DTC based on pathology reports of surgery samples. An additional 100 people were selected as a control group with no cancer history. PCR-HRM (high resolution melting) analysis was performed to deal with each of mutations in all case and control samples separately. During the analysis of $IVS2+1G{\rightarrow}A$ and Ile157Thr mutations of CHEK2 gene in the case and control groups, all the samples were identified as wild homozygote type. The finding suggests that $IVS2+1G{\rightarrow}A$ and Ile157Thr mutations of CHEK2 gene do not constitute a risk factor for DTC in the Iranian population. However, further studies with larger population are required to confirm the outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6653-6656
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• 2013

Background: The single most common proto-oncogene change in human neoplasms is a point mutation in RAS genes. A wide range of variation in frequency of KRAS mutations has been seen in hematologic malignancies. Despite this, RAS roles in leukemogenesis remain unclear. The frequency of KRAS mutations in CML has been reported to be between zero an 10%. Many attempts have been done to develop an anti-RAS drug as a therapeutic target. Materials and Methods: This cross sectional study was performed in Mashhad University of Medical Sciences, Mashhad, Iran from 2010-2012. In 78 CML patients (diagnosed according to WHO 2008 criteria) in chronic or accelerated phases, KRAS mutations in codons 12 and 13 were analyzed using a modified PCR-restriction fragment length polymorphism (RFLP) method. Results: We did not detect any KRAS mutations in this study. Conclusions: KRAS mutations are overall rare in early phase CML and might be secondary events happening late in leukemogenesis cooperating with initial genetic lesions.

• Parasites, Hosts and Diseases
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• v.60 no.2
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• pp.109-116
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• 2022

Drug resistance is an important problem hindering malaria elimination in tropical areas. Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes confer resistance to antifolate drug, sulfadoxine-pyrimethamine (SP) while P. falciparum chloroquine-resistant transporter (Pfcrt) genes caused resistance to chloroquine (CQ). Decline in Pfdhfr/Pfdhps and Pfcrt mutations after withdrawal of SP and CQ has been reported. The aim of present study was to investigate the prevalence of Pfdhfr, Pfdhps, and Pfcrt mutation from 2 endemic areas of Thailand. All of 200 blood samples collected from western area (Thai-Myanmar) and southern area (Thai-Malaysian) contained multiple mutations in Pfdhfr and Pfdhps genes. The most prevalent haplotypes for Pfdhfr and Pfdhps were quadruple and double mutations, respectively. The quadruple and triple mutations of Pfdhfr and Pfdhps were common in western samples, whereas low frequency of triple and double mutations was found in southern samples, respectively. The Pfcrt 76T mutation was present in all samples examined. Malaria isolated from 2 different endemic regions of Thailand had high mutation rates in the Pfdhfr, Pfdhps, and Pfcrt genes. These findings highlighted the fixation of mutant alleles causing resistance of SP and CQ in this area. It is necessary to monitor the re-emergence of SP and CQ sensitive parasites in this area.

• Anatomy and Cell Biology
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• v.56 no.1
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• pp.94-108
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• 2023

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1771-1774
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• 2014

The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS.