p53 mutation in hepatocellular carcinoma after aflatoxin exposure

Bressac, Brigitte; Puisieux, Alain; Kew, Michael C.; Volkmann, Martin; Bozcall, Sema; Mura, Jessika Bella; Monte, Suzanne de la; Carlson, Richard P.; Blum, Hubert E.; Wands, Jack R.; Takahashi, Hiroshi; Weizsäcker, Fritz von; Galun, E.; Kar, Siddhartha; Carr, Brian I.; Schroder, ClausH; Erken, Eren; Varinli, Seyhan; Rustgi, V.; Prat, Jaime; Toda, Gotaro; Koch, HerbertK; Liang, Xiao; Tang, Zhao–You; Shouval, Daniel; Lee, Hyo‐Suk; Vyas, Girish N.; Sarosi, Ildiko; Öztürk, Mehmet

doi:10.1016/0140-6736(91)92236-u

Cited by 373 publications

(42 citation statements)

References 12 publications

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“…In addition, AFB1 can induce 8-hydroxy-2'-deoxyguanosine, which also produces predominantly G > T mutations in in vitro experimental models [52]. The mutation signature of AFB1 has been primarily studied in the TP53 gene, and indeed particular somatic mutations in TP53 are used as biomarkers for aflatoxin exposure in tumors [55,56]. However, the extended mutation signature of AFB1 has not been studied (Table 1).…”

Section: Signatures Of Single Mutagensmentioning

confidence: 99%

Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention

et al. 2014

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Exposure to environmental mutagens is an important cause of human cancer, and measures to reduce mutagenic and carcinogenic exposures have been highly successful at controlling cancer. Until recently, it has been possible to connect the chemical characteristics of mutagens to actual mutations observed in human tumors only indirectly. Now, next-generation sequencing technology enables us to observe in detail the DNA-sequence-level effects of well-known mutagens, such as ultraviolet radiation and tobacco smoke, as well as endogenous mutagenic processes, such as those involving activated DNA cytidine deaminases (APOBECs). We can also observe the effects of less well-known but potent mutagens, including those recently found to be present in some herbal remedies. Crucially, we can now tease apart the superimposed effects of several mutational exposures and processes and determine which ones occurred during the development of individual tumors. Here, we review advances in detecting these mutation signatures and discuss the implications for surveillance and prevention of cancer. The number of sequenced tumors from diverse cancer types and multiple geographic regions is growing explosively, and the genomes of these tumors will bear the signatures of even more diverse mutagenic exposures. Thus, we envision development of wide-ranging compendia of mutation signatures from tumors and a concerted effort to experimentally elucidate the signatures of a large number of mutagens. This information will be used to link signatures observed in tumors to the exposures responsible for them, which will offer unprecedented opportunities for prevention.

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Section: Signatures Of Single Mutagensmentioning

confidence: 99%

Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention

et al. 2014

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“…Concurrent infection with HBV increases the risk of hepatocarcinogenesis induced by aflatoxin B by interfering with the ability of hepatocytes to metabolize aflatoxins [36]. A genetic hallmark of HCC caused by aflatoxin B is mutation of the p53 gene at codon 249 [37]. This mutation is much more frequent in areas where exposure to both HBV and aflatoxin B is prevalent, suggesting a possible synergistic effect of the two in inducing hepatocarcinogenesis [38,39,40].…”

Section: Molecular Mechanisms Of Hepatocarcinogenesismentioning

confidence: 99%

From Molecular Biology to Targeted Therapies for Hepatocellular Carcinoma: The Future Is Now

Pang¹,

2007

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Hepatocellular carcinoma (HCC) is characterized as a highly chemoresistant cancer with no effective systemic therapy. Despite surgical or locoregional therapies, prognosis remains poor because of high tumor recurrence or tumor progression, and currently there are no well-established effective adjuvant therapies. The molecular biology of carcinogenesis and tumor progression of HCC has been increasingly understood with intense research in recent years. Several important intracellular signaling pathways such as the Ras/Raf/Mek/Erk pathway and PI3k/Akt/mTOR pathway have been recognized, and the role of several growth factors and angiogenic factors such as EGF and VEGF has been confirmed. Effective agents targeting these molecular abnormalities have been developed and widely tested in preclinical studies of HCC cell lines or xenograft models. Several agents have entered clinical trials in HCC patients, and recent data indicated that a multikinase inhibitor targeting Ras kinase and VEGFR-2, sorafenib, is effective in prolonging survival of patients with advanced HCC. The management of advanced HCC is entering the era of molecular targeting therapy, which is of particular significance for HCC in view of the lack of existing effective systemic therapy for this cancer.

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“…Later, dietary aflatoxin intake was found to be associated with a codon 249 mutation of the p53 gene in an endemic form of HCC [27]. However, Unsal, et al [28] demonstrated that HBV also has an important role in the wild-type p53 function, and this mutation seems rare outside Mozambique, even in other places with a high incidence of HCC and aflatoxin contaminated food.…”

Section: Early Studies: Biomedical Researchmentioning

confidence: 99%

“…For example, Krishnappa, et al [51] tested the effect of garlic extract in the liver of Winstar rats damaged by aflatoxin B 1 and their results were satisfactory. Yet, this line of research is not likely to become a priority in Mozambique, though some key studies in the area were conducted in the country or based on the Mozambican population [1,25,27,29]. Among the reasons, the following can be considered: there is already some information on the matter in the country and much more locally known, though not available in the mainstream international literature.…”

Section: Perspectivesmentioning

confidence: 99%

A Glance at Aflatoxin Research in Mozambique

Cambaza

Koseki

Kawamura

2018

IJERPH

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In Mozambique, aflatoxin research started in the 1960’s and has been carried through apparently unrelated efforts according to opportunities. However, they can be grouped in two sets: early epidemiological studies and recent agricultural research. Early investigators found a strong correlation between aflatoxin contamination and primary liver cancer. Since then, there have been efforts to examine the extent of contamination, especially in groundnuts and maize. More recent investigations and interventions aimed mostly to reduce the level of contamination, enough to allow such commodities to gain acceptance in the international market. The current status of knowledge is still marginal but the increasing involvement of local authorities, academia, and international organizations seems promising.

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p53 mutation in hepatocellular carcinoma after aflatoxin exposure

Cited by 373 publications

References 12 publications

Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention

Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention

From Molecular Biology to Targeted Therapies for Hepatocellular Carcinoma: The Future Is Now

A Glance at Aflatoxin Research in Mozambique

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