Khan, S.A.; Taylor-Robinson, S.D.; Carmichael, P.L.; Habib, N.; Lemoine, N.; Thomas, H.C.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA32
Academic Journal
Background: Cholangiocarcinoma (CCa) may arise from cholangiocyte DNA damage due to genotoxic compounds in bile. We have previously shown that human biliary tissue is exposed to genotoxic agents, as evidenced by the presence of DNA adducts. The correlation of DNA lesions along a target gene with a known "mutational signature" induced by an environmental carcinogen is a means of linking cause and effect in human cancer. The tumour suppressor gene p53 is known to have 'hotspots' for particular chemical carcinogens. Previous studies of p53 mutation in CCa have focused on exons 5-8, potentially missing gene alterations at other sites. This study examined the link between environmental carcinogens and CCa, by analysing CCa DNA for complete p53 mutational signatures. Methods: Entire p53 cDNA (all exons) from 31 intrahepatic CCa patients were screened by single strand conformational polymorphism. Exons exhibiting aberrant bands were fully sequenced. Mutations were compared to known p53 mutations in CCa, and to mutations induced by environmental mutagens, as described in p53 databases. Results and Conclusions: Five non-silent p53 mutations were found, including an exon 5 missense and a nonsense mutation, both previously reported. Three frameshifis (2 deletions and 1 insertion) in exons 4, 5, and 6, and two intron mutations were discovered, none of which have been previously reported. No predominant mutational signature was seen. This may be due to host or environmental differences in study populations, lack of data outside exons 5-8, bias in mutation reporting or because non-coding regions or other genes are involved. Further epidemiological and molecular studies are required to establish risk factors and elucidate genotoxic and host mechanisms in cholangiocarcinoma.


Related Articles

  • Cytochrome P450 Gene Polymorphism and Cancer. Agtindez, Jos� A.G. // Current Drug Metabolism;Jun2004, Vol. 5 Issue 3, p211 

    Human cytochrome P450 (CYP) enzymes play a key role in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. Phenotyping analyses revealed an association between CYP enzyme activity and the risk to develop...

  • The role of gene conversion in determining sequence variation and divergence in the Est-5 gene... King, Lynn Mertens // Genetics;Jan98, Vol. 148 Issue 1, p305 

    Presents a study describing patterns of polymorphism and divergence in Est-5A, Est-5C and Est-5B gene family, while examining if gene conversion and how it contributes to sequence variation. Materials and methods used; Molecular characterization of the Est-5 gene region; Results and discussion...

  • Properties of statistical tests of neutrality for DNA polymorphism data. Simonsen, Katy L.; Churchill, Gary A. // Genetics;Sep95, Vol. 141 Issue 1, p413 

    Studies a class of statistical tests based on molecular polymorphism data to determine size and power properties. Results of neutral simulations; Results of selective sweep simulations; Results of population bottleneck simulations; Results of population subdivision simulations; Comments on...

  • Time-series analysis of seasonal changes of the O... Rodriguez-Trelles, Franciso; Alvarez, Gonzalo // Genetics;Jan96, Vol. 142 Issue 1, p179 

    States that due to a study of seasonal variation of inversion polymorphisms of the O chromosome of Drosophila subobscura in a natural population. Length of study; What all the common arrangements showed; Materials and methods; Seasonal frequencies of the O arrangements.

  • In Vitro Maintenance of Clonorchis sinensis Adult Worms. Uddin, Hafiz; Shunyu Li; Young Mee Bae; Min-Ho Choi; Sung-Tae Hong // Korean Journal of Parasitology;Dec2012, Vol. 50 Issue 4, p309 

    Clonorchis sinensis is a biological carcinogen inducing human cholangiocarcinoma, and clonorchiasis is one of the important endemic infectious diseases in East Asia. The present study investigated survival longevity of C. sinensis adult worms in various in vitro conditions to find the best way...

  • Carcinoma of the common bile duct with superficial spread... Kato, Masamichi; Nimura, Yuji // American Surgeon;Nov1997, Vol. 63 Issue 11, p943 

    Presents a case of a patient with bile duct carcinoma. Complaints of patient with bile duct carcinoma; Preoperative diagnosis and rational surgical treatment of bile duct carcinoma with superficial spread.

  • A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Esterbauer, Harald; Schneitler, Clemens; Oberkofler, Hannes; Ebenbichler, Christoph; Paulweber, Bernhard; Sandhofer, Friedrich; Ladurner, Gunther; Hell, Emanuel; Strosberg, A. Donny; Patsch, Josef R.; Krempler, Franz; Patsch, Wolfgang // Nature Genetics;Jun2001, Vol. 28 Issue 2, p178 

    Obesity is the most common nutritional disorder in Western society. Uncoupling protein-2 (UCP2) is a recently identified member of the mitochondrial transporter superfamily that is expressed in many tissues, including adipose tissue. Like its close relatives UCP1 and UCP3, UCP2 uncouples proton...

  • Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Huang, D; Cancilla, M R; Morahan, G // Genes & Immunity;Dec2000, Vol. 1 Issue 8, p515 

    Owing to the importance of interleukin (IL)-12 in regulating immune responses, we have determined the complete genomic sequence and organization of the gene encoding its p40 subunit. The genomic sequence was determined and was compared to cDNA sequences to derive exon/intron boundaries....

  • ACE Gene Polymorphism and Diabetic Complications: Is There a Connection? Kennon, B.; Connell, J.M.C. // BioDrugs;2000, Vol. 14 Issue 2, p73 

    The insertion/deletion (I/D) polymorphism of the ACE gene accounts for 50% of the variation in serum ACE levels and activity. However, its functional significance with regard to diabetic complications and cardiovascular disease remains controversial. To review the literature assessing the...


Read the Article


Sign out of this library

Other Topics