p53 mutations in British patients with hepatocellular carcinoma: Clustering in genetic hemochromatosis

Vautier, Guy; Bomford, Adrian; Portmann, Bernard; Metivier, Elizabeth M.; Williams, Roger; Ryder, Stephen D.

doi:10.1016/s0016-5085(99)70562-7

Cited by 83 publications

(29 citation statements)

References 24 publications

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“…In urothelial carcinomas this is the only hotspot associated with adenine substitution (Arlt et al 2001). Also, a clustering of A to G mutations at codon 220 has been reported in British patients with haemochromatotic hepatocellular carcinoma, possibly due to iron acting as a carcinogen (Vautier et al 1999).…”

Section: Discussionmentioning

confidence: 96%

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Dansonka-Mieszkowska

Ludwig

Kraszewska

et al. 2006

Annals of Human Genetics

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SummaryThe TP53 gene mutational spectrum in human tumours shows variations related to tissue of origin, carcinogen exposure or molecular background. We have compared TP53 mutations in ovarian carcinomas from different geographical regions; this study was based on data extracted and verified from the IARC database (R10, 2005), and on our results from 127 carcinomas. In total 873 mutations were evaluated. Tumours from Japan and Korea had a higher frequency of exon 7 mutations (38% vs 25%, p = 0.011) and lower frequency of exon 8 mutations (11% vs 29%, p = 0.0003) than those from Western countries; they were particularly different from Norwegian tumours which showed the lowest proportion of exon 7 (19%, p = 0.001) and highest proportion of exon 8 (37%, p < 0.0001) mutations. There were also differences in the profile of TP53 hotspots. The third hotspot in tumours from Poland was amino acid (AA) 176 (8.2% of substitutions vs 1.7% in other countries, p < 0.001), while in tumours from the UK it was AA 220 (8.9% vs 2.3%, p < 0.001). Codon 273 was the only apparent hotspot in the Norwegian tumours, while it was rarely mutated in Polish and Asian tumours. In contrast to other data tumours from Norway presented with 273 HIS codon (82% of mutations at AA 273, p = 0.002), while tumours from the UK shared the 273 CYS codon (80%, p < 0.001). Further analysis of TP53 gene mutations in ovarian cancer by geography could provide greater insights.

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Section: Discussionmentioning

confidence: 96%

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Dansonka-Mieszkowska

Ludwig

Kraszewska

et al. 2006

Annals of Human Genetics

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“…In contrast, patients who have not been exposed to this carcinogen have a lower prevalence of TP53 gene mutations (10-30%) and codon 249 is rarely altered. A second hotspot of mutations has been suggested in HCC occurring in patients with hereditary hemochromatosis, at codon 220 (Vautier et al, 1999), but this result is debated in other series (Laurent-Puig et al,…”

Section: Alterations Of the Tp53 Genementioning

confidence: 99%

Genetics of hepatocellular tumors

2006

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Numerous genetic alterations are accumulated during the process of hepatocarcinogenesis. These genetic alterations can be divided into two groups. The first set of genetic alterations is specific of hepatocellular tumor risk factors. It includes integration of hepatitis B virus (HBV) DNA, R249S TP53 (tumor protein p53) mutation in aflatoxin B1-exposed patients, KRAS mutations related to vinyl chloride exposure, hepatocyte nuclear factor 1a (HNF1a) mutations associated to hepatocellular adenomas and adenomatosis polyposis coli (APC) germline mutations predisposing to hepatoblastomas. The second set of genetic alterations are etiological nonspecific, it includes recurrent gains and losses of chromosomes, alteration of TP53 gene, activation of WNT/b-catenin pathway through CTNNB1/b-catenin and AXIN (axis inhibition protein) mutations, inactivation of retinoblastoma and IGF2R (insulin-like growth factor 2 receptor) pathways through inactivation of RB1 (retinoblastoma 1), P16 and IGF2R. Comprehensive analyses of these genetic alterations have defined two pathways of hepatocarcinogenesis according to the presence or the absence of chromosomal instability. Hepatitis B virus and poorly differentiated tumors are related to chromosome instable tumors associated with frequent TP53 mutations, whereas non-HBV and well-differentiated tumors are related to chromosomal stable samples that are frequently b-catenin activated. These classifications have clinical relevance as genetic alterations may also be related to prognosis.

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“…HNE has the potential to damage genomic DNA and cause mutations, e.g., HNE adduct has been demonstrated to cause p53 mutations which are associated with more than 50% of HCC incidences [43] . A more important link was discovered in patients with hemochromatosis who suffered iron overload and p53 mutations following HCC development [41,[44][45][46] ; it suggests that oxidative stress is an underlying mechanism of HCC carcinogenesis [44] . The role of oxidative stress in liver carcinogenesis is also supported by the result of a multicenter study: using tissue microarray screening, cytochrome P450 1A2 (CYP1A2) oxidase in noncancerous tissue is found and validated as the only predictive factor for HCC recurrence [47] .…”

Section: Hepatatocarcinogenesis and Oxidative Stressmentioning

confidence: 99%

Oxidative stress and hepatocarcinogenesis

Chung

2018

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. There are two major challenges for HCC, the first being that early detection is generally not applicable, and secondly, it is usually fatal within several months after diagnosis. HCC is an inflammation-induced cancer. It is known that chronic inflammation leads to oxidative/nitrosative stress and lipid peroxidation, generating excess oxidative stress, together with aldehydes which can react with DNA bases to form promutagenic DNA adducts. In this review, the evidence between oxidative stress and liver carcinogenesis is summarized. We focused on the potential of using DNA adducts as oxidative stress biomarkers for liver carcinogenesis.

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p53 mutations in British patients with hepatocellular carcinoma: Clustering in genetic hemochromatosis

Cited by 83 publications

References 24 publications

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Genetics of hepatocellular tumors

Oxidative stress and hepatocarcinogenesis

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