• Title/Summary/Keyword: somatic mutation

Search Result 29, Processing Time 0.106 seconds

Mitochondrial DNA Somatic Mutation in Cancer

  • Kim, Aekyong
    • Toxicological Research
    • /
    • v.30 no.4
    • /
    • pp.235-242
    • /
    • 2014
  • Cancer cells are known to drastically alter cellular energy metabolism. The Warburg effect has been known for over 80 years as pertaining cancer-specific aerobic glycolysis. As underlying molecular mechanisms are elucidated so that cancer cells alter the cellular energy metabolism for their advantage, the significance of the modulation of metabolic profiles is gaining attention. Now, metabolic reprogramming is becoming an emerging hallmark of cancer. Therapeutic agents that target cancer energy metabolism are under intensive investigation, but these investigations are mostly focused on the cytosolic glycolytic processes. Although mitochondrial oxidative phosphorylation is an integral part of cellular energy metabolism, until recently, it has been regarded as an auxiliary to cytosolic glycolytic processes in cancer energy metabolism. In this review, we will discuss the importance of mitochondrial respiration in the metabolic reprogramming of cancer, in addition to discussing the justification for using mitochondrial DNA somatic mutation as metabolic determinants for cancer sensitivity in glucose limitation.

Germinal Center-independent Affinity Maturation in Tumor Necrosis Factor Receptor 1-deficient Mice

  • Kim, Jin-Ho;Kim, Ju;Jang, Yong-Suk;Chung, Gook-Hyun
    • BMB Reports
    • /
    • v.39 no.5
    • /
    • pp.586-594
    • /
    • 2006
  • Germinal centers (GCs) have been identified as site at which the somatic mutation of immunoglobulins occurs. However, somatic mutations in immunoglobulins have also been observed in animals that normally do not harbor germinal centers. This clearly indicates that somatic mutations can occur in the absence of germinal centers. We therefore attempted to determine whether or not GCs exist in TNFR1-deficient mice, and are essential for the somatic mutation of immunoglobulins, using (4-hydroxy-3-nitropheny)acetyl-ovalbumin (NP-OVA). Both wild-type and TNFR1-deficient mice were immunized with NPOVA, and then examined with regard to the existence of GCs. No typical B-cell follicles were detected in the TNFR1-deficient mice. Cell proliferation was detected throughout all splenic tissue types, and no in vivo immune-complex retention was observed in the TNFR1-deficient mice. All of these data strongly suggest that no GCs were formed in the TNFR1-deficient mice. Although TNFR1-deficient mice are unable to form GCs, serological analyses indicated that affinity maturation had been achieved in both the wild-type and TNFR1-deficient mice. We therefore isolated and sequenced several DNA clones from wild-type and the TNFR1-deficient mice. Eight out of 12 wild-type clones, and 11 out of 14 clones of the TNFR-1-deficient mice contained mutations at the CDR1 site. Thus, the wild-type and TNFR1-deficient mice were not extremely different with regard to types and rates of somatic mutation. Also, high-affinity antibodies were detected in both types of mice. Collectively, our data appear to show that affinity maturation may occur in TNFR1-deficient mice, which completely lack GCs.

Analysis of p53 Somatic Mutation in Head and Neck Cancer Using Denaturing High Performance Liquid Chromatography(DHPLC) (두경부 종양에서 DHPLC를 이용한 p53체세포 돌연변이 검출 연구)

  • Kim, Kwang-Youl;Park, Sang-Bum;Han, Sang-Man;Nam, Youn-Hyoung;Jang, Won-Cheoul
    • Journal of the Korean Chemical Society
    • /
    • v.48 no.1
    • /
    • pp.33-38
    • /
    • 2004
  • Mutation of p53 tumor suppressor gene in HNSCC (head and neck squamous cell carcinoma) has been proposed high rate. We extracted genomic DNA from 50 head and neck cancer. The DNA was amplified by PCR at exon 5-8 in p53 tumor suppressor gene. We have compared single strand conformation polymorphism (SSCP) and denaturing high performance liquid chromatography (DHPLC) method for analysis of p53 somatic mutation. As a result, 16 deleted mutations (32%) were detected by SSCP analysis and 17 deleted mutations (34%) were detected by DHPLC analysis at exon 8. All of 17 mutations were proved by sequencing. We conclude that DHPLC is a fast and simple screening method rather than SSCP analysis.

Mutagenicity Studies of Cosmetic Dyes (2) (외용색소의 유전독성에 관한 연구(2))

  • 하광원;김명희;오혜영;허옥순;한의식
    • Journal of Food Hygiene and Safety
    • /
    • v.13 no.2
    • /
    • pp.135-142
    • /
    • 1998
  • The mutagenicity of three external colorants, lake red CBA (D&C Red No.9, R-9), rhodamine B stearate (D&C Red No.37, R-37) and permanent orange (D&C Orange No.17, O-17) was evaluated. In this study, the genetic toxicity of the these dyes was examined by in vitro chromosome aberration test in cultured mammalian cells, in vivo micronucleus test in ddY mice, and somatic mutation and recombination test (SMART) in Drosophila melanogaster. Three dyes did not induce mutagenicity in chromosome aberration test and micronucleus test. But Red No.9 and Red No. 37 showed slight increase of abnormal wing spots in Drosophila melanogaster.

  • PDF

Comparison of Mutant Frequencies Induced by ${\gamma}$-radiation and Pentachlorophenol at hprt Locus in Human T-lymphocytes(I) (인체 T-림프구 hprt 유전자에서 방사선 및 pentachlorophenol에 의한 돌연변이 빈도의 비교(I))

  • Kim, In-Gyu;Park, Seon-Young;Yoon, Byung-Su;Cho, Myung-Haing;Lee, Yong-Soon
    • Journal of Radiation Protection and Research
    • /
    • v.22 no.1
    • /
    • pp.15-21
    • /
    • 1997
  • In vitro somatic mutation induced by ${\gamma}$-radiation and pentachlorophenol(PCP) which is representative of chemical pollutant was measured at the hypoxanthine-guanine phosphoribosyl transferase(hprt) locus in human T- lymphocytes by a cell cloning assay. Mutant cells were selected by their ability to form a clone in the presence of purine analogue 6-thioguanine. The mutant frequencies by ${\gamma}$-irradiation to a dose of 1.0 Gy, 2.0 Gy and 3.0 Gy were 40%, 400% and 750% higher than those in controls. Significant changes were not observed in mutant frequencies in the 0.2 Gy and 0.5 Gy irradiated groups. When the doses of PCP were 15 ppm, 25 ppm and 50 ppm, the mutant frequencies increased by 30%, 90% and 520%, respectively. No changes were observed in the 10 ppm treated group. Similar types of dose-response relationship were shown in the two different mutagens. Reverse transcriptase/polymerase chain reaction technique(RT/PCR) was needed for the mutation spectrum to discriminate combined exposure to radiation and chemicals.

  • PDF

Somatic Mutations of the ENPP2 (Autotaxin/lysoPLD) Gene in Breast Cancer

  • Song, Jae-Hwi;Kim, Jeong-Kyu;Noh, Ji-Heon;Jung, Kwang-Hwa;Eun, Jung-Woo;Kim, Chang-Jae;Bae, Hyun-Jin;Xie, Hong-Jian;Ahn, Young-Min;Lee, Sug-Hyung;Yoo, Nam-Jin;Lee, Jung-Young;Park, Won-Sang;Nam, Suk-Woo
    • Molecular & Cellular Toxicology
    • /
    • v.3 no.4
    • /
    • pp.262-266
    • /
    • 2007
  • ENPP2, a 125 kDa secreted lysophopholipase D which originally identified as a tumor-motogen, Autotaxin, enhances cellular locomotion, cell proliferation, angiogenesis and cell survival by generating the signal molecule lysophosphatic acid or sphingosine-1-phosphate. Previous studies have suggested that expression of Autotaxin is associated with invasive phenotype in advanced breast carcinomas. Thus, to determine whether genetic alterations of ENPP2 gene are involved in the development or progression of breast cancer, we analyzed its somatic mutation in 85 breast carcinomas by single-stranded conformational polymorphism and sequencing. Overall, six ENPP2 mutations were found (7.0%), comprising five missense and one nonsense mutation (s). To our knowledge, this is the first report on ENPP2 mutation in breast carcinoma, and the data indicate that ENPP2 is occasionally mutated in breast carcinomas, and suggest that ENPP2 mutation may contribute to the tumor development in some breast carcinomas.

Mutational Analysis of Proapoptotic Bcl-2 Family Members in Gastric Carcinomas (위암에서의 고사유발성 Bcl-2 Family의 돌연변이에 관한 연구)

  • Yoo Nam Jin;Lee Jong Woo;Soung Young Hwa;Kim Hong Sug;Park Won Sang;Lee Jung Young;Lee Sug Hyung
    • Journal of Gastric Cancer
    • /
    • v.3 no.2
    • /
    • pp.84-87
    • /
    • 2003
  • Purpose: Evidence exists that dysregulation of Bcl-2 family members is involved in the pathogenesis of cancer development. The aim of this study was to explore whether the somatic mutation of proapoptotic Bcl-2 member genes, one of the mechanisms that prolong the survival of cancer cells, is involved in gastric carcinogenesis. Materials and Methods: In the current study, to detect somatic mutations of the DNA sequences encoding the Bcl-2 homology 3 (BH3) domain of the human BAD, BIM, BIK, and Bcl-G genes in 60 advanced gastric adenocarcinomas, we used the polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing. Results: The SSCP analysis revealed no mutations in the coding regions of the BH3 domain in the cancers. Conclusion: The data presented here indicate that proapoptotic Bcl-2 member genes, BAD, BIM, BIK, and Bcl-G, may not be mutated in human gastric carcinomas and suggest that these genes might be altered by mechanisms other mechanisms somatic mutation.

  • PDF

Genotype-Calling System for Somatic Mutation Discovery in Cancer Genome Sequence (암 유전자 배열에서 체세포 돌연변이 발견을 위한 유전자형 조사 시스템)

  • Park, Su-Young;Jung, Chai-Yeoung
    • Journal of the Korea Institute of Information and Communication Engineering
    • /
    • v.17 no.12
    • /
    • pp.3009-3015
    • /
    • 2013
  • Next-generation sequencing (NGS) has enabled whole genome and transcriptome single nucleotide variant (SNV) discovery in cancer and method of the most fundamental being determining an individual's genotype from multiple aligned short read sequences at a position. Bayesian algorithm estimate parameter using posterior genotype probabilities and other method, EM algorithm, estimate parameter using maximum likelihood estimate method in observed data. Here, we propose a novel genotype-calling system and compare and analyze the effect of sample size(S = 50, 100 and 500) on posterior estimate of sequencing error rate, somatic mutation status and genotype probability. The result is that estimate applying Bayesian algorithm even for 50 of small sample size approached real parameter than estimate applying EM algorithm in small sample more accurately.

Brain somatic mutations in MTOR leading to focal cortical dysplasia

  • Lim, Jae Seok;Lee, Jeong Ho
    • BMB Reports
    • /
    • v.49 no.2
    • /
    • pp.71-72
    • /
    • 2016
  • Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients.

Studies on the Genotoxicity of the Gamma-irradiated Panax Ginseng Radix In Vitro and In Vivo (방사선조사 인삼의 유전독성에 관한 연구)

  • 하광원;정해관;오혜영;허옥순;손수정;한의식;정성철;최부영;김영미
    • Journal of Food Hygiene and Safety
    • /
    • v.9 no.2
    • /
    • pp.67-74
    • /
    • 1994
  • This study was aimed to find out the comparative effects between non-irradiated, and 5kGy-10kGy of gamma-irradiated Panax Ginseng Radix powder on the genotoxicity for identification of possibility of DNA damage causing cancer. Four different short-term mutagenicity tests were used: (1) Salmonella typhimurium reversion assay (Ames test) (2) Chromosome aberration test in cultured Chinese hamster lung (CHL) fibroblast cells. (3) Micronucleus test in ddY mouse (4) Somatic mutation and recombination test in the wing cells of Drosophila melanogaster.Gamma-irradiated Panax Ginseng Radix powder revealed negative results in these four mutagenicity tests. This means gamma-irradiated ginseng could be safe on the genotoxic point of view.

  • PDF