Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

Laurent‐Puig, Pierre; Legoix, Patricia; Bluteau, Olivier; Belghiti, Jacques; Franco, Dominique; Binot, Frederic; Monges, Geneviève; Thomas, Gilles; Bioulac‐Sage, Paulette; Zucman‐Rossi, Jessica

doi:10.1053/gast.2001.24798

Cited by 525 publications

(477 citation statements)

References 35 publications

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“…71 Mutations of the p53 gene on chromosome 17 have been frequently found in primary liver cancer. [72][73][74] This hotspot mutation was originally described in HCC from regions with high levels of dietary aflatoxins, and is considered a hallmark of AFB1. The molecular and cellular mechanisms underlying the carcinogenic effects of aflatoxin have also been investigated on numerous occasions in rodent models.…”

Section: Role Of Aflatoxin B Causes Hepatocellular Carcinoma In Indiamentioning

confidence: 99%

Risk Factors for Hepatocellular Carcinoma in India

Kar

2014

Journal of Clinical and Experimental Hepatology

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Hepatocellular carcinoma (HCC) is an important cause of death all over the world, more so in Asia and Africa. The representative data on epidemiology of HCC in India is very scanty and cancer is not a reportable disease in India and the cancer registries in India are mostly urban. 45 million people who are suffering from chronic Hepatitis B virus (HBV) infection and approximately 15 million people who are afflicted with chronic Hepatitis C virus (HCV) infection in India. HBV and HCV infection is considered an important etiologic factor in HCC. Positive association between HCC and consumption of alcohol where alcohol contribute as a cofactor for hepatotoxins and hepatitis viruses. Aflatoxin contamination in the diets, Hepatitis B virus infection and liver cirrhosis in Andhra Pradesh, India and direct chronic exposure to aflatoxins was shown to cause liver cirrhosis. Cirrhosis of liver of any cause lead to develop about 70%-90% of HCC. Aflatoxin interact synergistically with Hepatitis B virus (HBV)/Hepatitis C virus (HCV) infection which increase the risk of HCC. HBV infection, HBV infection with Aflatoxin exposure, viral infection and alcohol consumption leading to overt cirrhosis of the liver, alcohol consumption leading to cirrhosis of the liver with viral infection are the predominant risk factor for the development of HCC. HCV and alcohol are also associated with HCC in India. Indians develop diabetes at younger age, Asians have strong genetic susceptibility for type II diabetes. Diabetes mellitus is identified as a risk factor for HCC. Prevention of viral infection by universal vaccination against hepatitis virus, HCC surveillance program, preventing alcoholic liver diseases, fungal contamination of grains and ground crops to prevent basically Aflatoxin exposure are important measures to prevent liver diseases and HCC among those at risk. ( J CLIN EXP HEPATOL 2014;4:S34-S42)

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Section: Role Of Aflatoxin B Causes Hepatocellular Carcinoma In Indiamentioning

confidence: 99%

Risk Factors for Hepatocellular Carcinoma in India

Kar

2014

Journal of Clinical and Experimental Hepatology

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“…Myc/Tgfa mice have a typically poor prognosis phenotype, such as an earlier and higher incident rate of HCC development, higher mortality, higher genomic instability and higher expression of poor prognostic marker (Sargent et al, 1999;Calvisi et al, 2004). Myc and Myc/E2f1 mice have a relatively higher mutation frequency of and nuclear accumulation of b-catenin (Calvisi et al, 2001(Calvisi et al, , 2004, which in human HCC are indicative of lower genomic instability and better prognosis (Hsu et al, 2000;Laurent-Puig et al, 2001;Mao et al, 2001;Wong et al, 2001). The fact that these findings are first uncovered by using unsupervised methods and validated later using supervised methods indicates that the underlying principles in gene expression changes are conserved between mouse and human HCC.…”

Section: Comparative Functional Genomicsmentioning

confidence: 99%

Comparative and integrative functional genomics of HCC

2006

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Global gene expression profiling of hepatocellular carcinoma (HCC) is a promising new technology that has already refined the diagnosis and prognostic predictions of HCC patients. This has been accomplished by identifying genes whose expression pattern is associated with clinicopathological features of HCC tumors. Molecular characterization of HCC from gene expression profiling studies will undoubtedly improve the prediction of treatment responses, selection of treatments for specific molecular subtypes of HCC and ultimately the clinical outcome of HCC patients. The research focus is now shifting toward the identification of genetic determinants that are components of the specific regulatory pathways altered in cancers, and that may constitute novel therapeutic targets. Here we review the recent advances in gene expression profiling of HCC and discuss the future strategies for analysing large and complicated data sets from microarray studies and how to integrate these with diverse genomic data.

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“…It accelerates phosphorylation and ubiquitination of b-catenin, thus inhibiting importation of b-catenin to the nucleus and controlling cell proliferation. Although an association of Axin with carcinogenesis has been reported in colon cancer cell lines (Webster et al, 2000), HCC Laurent-Puig et al, 2001) and medulloblastoma (Dahmen et al, 2001), to our knowledge there has been no report concerning oesophageal SCC. Therefore, we investigated the association between Axin expression and oesophageal SCC.…”

Section: Discussionmentioning

confidence: 87%

“…AXIN1 mutations have been reported in a colon carcinoma cell line (Webster et al, 2000), hepatocellular carcinoma (HCC) Laurent-Puig et al, 2001), ovarian endometrioid adenocarcinoma (Wu et al, 2001), and sporadic medulloblastoma (Dahmen et al, 2001). In HCC cell lines with AXIN1 mutations, accumulation of b-catenin in the cytoplasm or nucleus has been observed, and the transcription activity of TCF4 is regulated positively .…”

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confidence: 99%

Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma

et al. 2003

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Axin is a negative regulator of the Wnt signalling pathway, and genetic alterations of AXIN1 have been suggested to be an important factor of carcinogenesis in some tumours. The objective of this study was to clarify the clinicopathologic and prognostic significance of Axin in oesophageal squamous cell carcinoma (SCC). Immunohistochemical staining for Axin was performed on surgical specimens obtained from 81 patients with oesophageal SCC. Western and Northern blottings were performed on proteins and RNA from oesophageal SCC cell lines. Then polymerase chain reaction -single-strand conformational analysis (PCR -SSCP) was performed on DNA from oesophageal SCC patients and cell lines. Axin expression was found to be correlated inversely with depth of invasion, lymph node metastasis, and lymphatic invasion. Although univariate analysis showed Axin to be a negative predictor, multivariate analysis showed that it was not an independent prognostic marker. In all but one of the seven cell lines examined, the levels of protein expression were equivalent to RNA expression. PCR -SSCP showed that five patients and three cell lines had polymorphisms in exon 4 or 5 of the AXIN1 gene, but none of the 81 patients with oesophageal SCC had mutations. Our findings suggest that reduced expression of Axin is correlated with tumour progression of oesophageal SCC. However, additional studies will be necessary to elucidate the mechanism responsible for loss of Axin expression in tumour cells.

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Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

Cited by 525 publications

References 35 publications

Risk Factors for Hepatocellular Carcinoma in India

Risk Factors for Hepatocellular Carcinoma in India

Comparative and integrative functional genomics of HCC

Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma

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