Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. It has been shown that, after HBV/HCV infection and alcohol or aflatoxin B1 exposure, genetic and epigenetic changes occur. The recurrent mutated genes were found to be highly enriched in multiple key driver signaling processes, including telomere maintenance, TP53, cell cycle regulation, the Wnt/beta-catenin pathway (CTNNB1 and AXIN1),  the phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Recent studies using whole-exome sequencing have revealed recurrent mutations in new driver genes involved in the chromatin remodelling (ARID1A and ARID2) and the oxidative stress (NFE2L2) pathways.

Cancer

TGFA (overexpression) [HSA:7039] [KO:K08774]
IGF2 (overexpression) [HSA:3481] [KO:K13769]
IGF1R (overexpression) [HSA:3480] [KO:K05087]
MYC (amplification) [HSA:4609] [KO:K04377]
RB1 (loss) [HSA:5925] [KO:K06618]
TERT (overexpression) [HSA:7015] [KO:K11126]
TP53 (mutation) [HSA:7157] [KO:K04451]
p16 (deletion)  [HSA:1029] [KO:K06621]
PTEN (mutation) [HSA:5728] [KO:K01110]
TGFBR2 (reduced expression) [HSA:7048] [KO:K04388]
FZD7 (overexpression) [HSA:8324] [KO:K02432]
CTNNB1 (mutation) [HSA:1499] [KO:K02105]
AXIN1 (mutation) [HSA:8312] [KO:K02157]
KEAP1 (mutation) [HSA:9817] [KO:K10456]
NFE2L2 (mutation) [HSA:4780] [KO:K05638]
HGF (overexpression) [HSA:3082] [KO:K05460]
MET (mutation, overexpression) [HSA:4233] [KO:K05099]
PIK3CA (mutation) [HSA:5290] [KO:K00922]
ARID1A (mutation) [HSA:8289] [KO:K11653]
ARID2 (mutation) [HSA:196528] [KO:K11765]

Aflatoxins (naturally occurring mixtures of) [CPD:C06800]
Alcoholic beverages
Opisthorchis viverrini (infection with)
Radium-224 and its decay products [CPD:C16455]
*Chimney sweeping
*2,3,7,8-Tetrachlorodibenzo-para-dioxin [CPD:C07557]
*Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium232 dioxide
*Tobacco smoking and tobacco smoke
*: Although this is a risk factor for liver cancer in general, the strength of association with different histological tumor types is not well understood.

Hepatitis B virus [GN:T40004]
Hepatitis C virus [GN:T40066]

Nivolumab [DR:D10316]
Sorafenib tosylate [DR:D06272]

ICD-O: 8170/3, Tumor type: Hepatocellular carcinoma (liver cell carcinoma)

PMID:21829020 (description, gene)

Kudo M

Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma.

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PMID:27895396 (description, gene)

Niu ZS, Niu XJ, Wang WH

Genetic alterations in hepatocellular carcinoma: An update.

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PMID:16799620 (gene)

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PMID:20639898 (gene)

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PMID:19387255 (gene)

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Pathogenesis of hepatocellular carcinoma and molecular therapies.

Curr Opin Gastroenterol 25:186-94 (2009)
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PMID:15085488

Suriawinata A, Xu R

An update on the molecular genetics of hepatocellular carcinoma.

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PMID:21251164 (gene)

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PMID:22348534 (gene)

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PMID:22561517 (gene)

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Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.

Nat Genet 44:694-8 (2012)
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PMID:27508192 (gene)

Granito A, Guidetti E, Gramantieri L

c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

J Hepatocell Carcinoma 2:29-38 (2015)
DOI:10.2147/JHC.S77038

PMID:15608678 (gene)

Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH

PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas.

Oncogene 24:1477-80 (2005)
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PMID:22922871 (gene)

Huang J, Deng Q, Wang Q, Li KY, Dai JH, Li N, Zhu ZD, Zhou B, Liu XY, Liu RF, Fei QL, Chen H, Cai B, Zhou B, Xiao HS, Qin LX, Han ZG

Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma.

Nat Genet 44:1117-21 (2012)
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PMID:23887712 (gene)

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High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions.

Nat Commun 4:2218 (2013)
DOI:10.1038/ncomms3218

PMID:17295177 (gene, tumor type)

Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM.

Genomics and signaling pathways in hepatocellular carcinoma.

Semin Liver Dis 27:55-76 (2007)
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PMID:11935086 (gene, tumor type)

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Pathology and pathogenesis of hepatocellular carcinoma.

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PMID:17051452 (tumor type)

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Serum markers of hepatocellular carcinoma.

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DOI:10.1055/s-2006-951606

PMID:12149612 (gene)

Thorgeirsson SS, Grisham JW.

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Nat Genet 31:339-46 (2002)
DOI:10.1038/ng0802-339

PMID:15760280 (carcinogen)

Schottenfeld D, Beebe-Dimmer JL.

Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions.

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PMID:15757802 (carcinogen)

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Epidemiology and natural history of hepatocellular carcinoma.

Best Pract Res Clin Gastroenterol 19:3-23 (2005)
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PMID:15489140 (carcinogen)

Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.

Environmental and chemical carcinogenesis.

Semin Cancer Biol 14:473-86 (2004)
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PMID:11285186 (carcinogen)

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The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis.

Carcinogenesis 22:535-45 (2001)
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PMID:15928434 (carcinogen)

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Association of parasitic infections and cancers.

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PMID:10564925 (carcinogen)

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Malignancies in patients treated with high doses of radium-224.

Radiat Res 152:S3-7 (1999)
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PMID:9498904 (carcinogen)

Boffetta P, Jourenkova N, Gustavsson P.

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.

Cancer Causes Control 8:444-72 (1997)

PMID:15660110 (carcinogen)

Luch A.

Nature and nurture - lessons from chemical carcinogenesis.

Nat Rev Cancer 5:113-25 (2005)
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PMID:12556326 (carcinogen)

Harrison JD, Muirhead CR.

Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.

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McGraw Hill Education