| H00048 | |
| H番号 | H00048 |
| 名称 | 肝細胞癌; 肝癌 |
| 概要 | 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. |
| カテゴリ | がん 疾患パスウェイ hsa05225 肝細胞癌 |
| ネットワーク | nt06110(H00048) MAPK signaling (viruses and bacteria) nt06114(H00048) PI3K signaling (viruses) nt06122(H00048) IFN signaling (viruses) nt06123(H00048) TNF signaling (viruses and bacteria) nt06124(H00048) Chemokine signaling (viruses) nt06130(H00048) Cell cycle (viruses) nt06131(H00048) Apoptosis (viruses and bacteria) nt06133(H00048) RLR signaling (viruses) nt06137(H00048) OAS/RNase L pathway (viruses) nt06140(H00048) Transcription (viruses) nt06162 Hepatitis B virus (HBV) nt06163 Hepatitis C virus (HCV) nt06263 Hepatocellular carcinoma nt06505(H00048) WNT signaling nt06507(H00048) TGFB signaling nt06516(H00048) TNF signaling nt06517(H00048) TLR signaling nt06518(H00048) JAK-STAT signaling nt06519(H00048) RLR signaling nt06524(H00048) Apoptosis nt06526(H00048) MAPK signaling nt06528(H00048) Calcium signaling nt06530(H00048) PI3K signaling |
| 病因遺伝子 | TGFA (overexpression) [HSA:7039] [KO:K08774] IGF2 (overexpression) [HSA:3481] [KO:K13769] IGF1R (overexpression) [HSA:3480] [KO:K05087] TERT (overexpression) [HSA:7015] [KO:K11126] FZD7 (overexpression) [HSA:8324] [KO:K02432] HGF (overexpression) [HSA:3082] [KO:K05460] MET (mutation, overexpression) [HSA:4233] [KO:K05099] MYC (amplification) [HSA:4609] [KO:K04377] RB1 (loss) [HSA:5925] [KO:K06618] CDKN2A (deletion) [HSA:1029] [KO:K06621] TGFBR2 (reduced expression) [HSA:7048] [KO:K04388] TP53 [HSA:7157] [KO:K04451] PTEN [HSA:5728] [KO:K01110] CTNNB1 [HSA:1499] [KO:K02105] AXIN1 [HSA:8312] [KO:K02157] KEAP1 [HSA:9817] [KO:K10456] NFE2L2 [HSA:4780] [KO:K05638] PIK3CA [HSA:5290] [KO:K00922] ARID1A [HSA:8289] [KO:K11653] ARID2 [HSA:196528] [KO:K11765] CASP8 [HSA:841] [KO:K04398] IGF2R [HSA:3482] [KO:K06564] |
| 病原体 | Hepatitis B virus [GN:T40004] Hepatitis C virus [GN:T40066] |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | マイトマイシンC [DR:D00208] シクロホスファミド水和物 [DR:D00287] ニムスチン塩酸塩 [DR:D01059] フルオロウラシル [DR:D00584] シタラビン [DR:D00168] テガフール・ウラシル [DR:D02131] ドキソルビシン塩酸塩 [DR:D01275] エピルビシン塩酸塩 [DR:D02214] ミトキサントロン塩酸塩 [DR:D02166] ソラフェニブトシル酸塩 [DR:D06272] レゴラフェニブ水和物 [DR:D10137] カボザンチニブリンゴ酸塩 [DR:D10095] レンバチニブメシル酸塩 [DR:D09920] デュルバルマブ [DR:D10808] アテゾリズマブ [DR:D10773] ベバシズマブ [DR:D06409] ラムシルマブ [DR:D09371] トレメリムマブ [DR:D06657] シスプラチン [DR:D00275] ミリプラチン水和物 [DR:D06294] |
| コメント | - |
| リンク | ICD-11: 2C12.0 ICD-10: C22 MeSH: D006528 OMIM: 114550 |
| 文献 | PMID:21829020 著者 Kudo M タイトル Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma. 雑誌 Dig Dis 29:289-302 (2011) DOI:10.1159/000327562 PMID:27895396 著者 Niu ZS, Niu XJ, Wang WH タイトル Genetic alterations in hepatocellular carcinoma: An update. 雑誌 World J Gastroenterol 22:9069-9095 (2016) DOI:10.3748/wjg.v22.i41.9069 PMID:16799620 著者 Breuhahn K, Longerich T, Schirmacher P タイトル Dysregulation of growth factor signaling in human hepatocellular carcinoma. 雑誌 Oncogene 25:3787-800 (2006) DOI:10.1038/sj.onc.1209556 PMID:20639898 著者 Whittaker S, Marais R, Zhu AX タイトル The role of signaling pathways in the development and treatment of hepatocellular carcinoma. 雑誌 Oncogene 29:4989-5005 (2010) DOI:10.1038/onc.2010.236 PMID:19387255 著者 Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM タイトル Pathogenesis of hepatocellular carcinoma and molecular therapies. 雑誌 Curr Opin Gastroenterol 25:186-94 (2009) DOI:10.1097/MOG.0b013e32832962a1 PMID:15085488 著者 Suriawinata A, Xu R タイトル An update on the molecular genetics of hepatocellular carcinoma. 雑誌 Semin Liver Dis 24:77-88 (2004) DOI:10.1055/s-2004-823102 PMID:22922871 著者 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 タイトル Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. 雑誌 Nat Genet 44:1117-21 (2012) DOI:10.1038/ng.2391 PMID:17295177 著者 Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM. タイトル Genomics and signaling pathways in hepatocellular carcinoma. 雑誌 Semin Liver Dis 27:55-76 (2007) DOI:10.1055/s-2006-960171 PMID:11935086 著者 Rocken C, Carl-McGrath S. タイトル Pathology and pathogenesis of hepatocellular carcinoma. 雑誌 Dig Dis 19:269-78 (2001) DOI:10.1159/000050693 PMID:12149612 著者 Thorgeirsson SS, Grisham JW. タイトル Molecular pathogenesis of human hepatocellular carcinoma. 雑誌 Nat Genet 31:339-46 (2002) DOI:10.1038/ng0802-339 PMID:21251164 (KEAP1, NFE2L2) 著者 Taguchi K, Motohashi H, Yamamoto M タイトル Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. 雑誌 Genes Cells 16:123-40 (2011) DOI:10.1111/j.1365-2443.2010.01473.x PMID:22348534 (KEAP1, NFE2L2) 著者 Yoo NJ, Kim HR, Kim YR, An CH, Lee SH タイトル Somatic mutations of the KEAP1 gene in common solid cancers. 雑誌 Histopathology 60:943-52 (2012) DOI:10.1111/j.1365-2559.2012.04178.x PMID:22561517 (CTNNB1, AXIN1, ARID1A, ARID2) 著者 Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, Clement B, Balabaud C, Chevet E, Laurent A, Couchy G, Letouze E, Calvo F, Zucman-Rossi J タイトル Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. 雑誌 Nat Genet 44:694-8 (2012) DOI:10.1038/ng.2256 PMID:27508192 (MET) 著者 Granito A, Guidetti E, Gramantieri L タイトル c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma. 雑誌 J Hepatocell Carcinoma 2:29-38 (2015) DOI:10.2147/JHC.S77038 PMID:15608678 (PIK3CA) 著者 Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH タイトル PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. 雑誌 Oncogene 24:1477-80 (2005) DOI:10.1038/sj.onc.1208304 PMID:23887712 (TERT) 著者 Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, Laurent C, Laurent A, Cherqui D, Balabaud C, Zucman-Rossi J タイトル High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. 雑誌 Nat Commun 4:2218 (2013) DOI:10.1038/ncomms3218 PMID:15531912 (CASP8) 著者 Soung YH, Lee JW, Kim SY, Sung YJ, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH タイトル Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas. 雑誌 Oncogene 24:141-7 (2005) DOI:10.1038/sj.onc.1208244 PMID:7493029 (IGF2R) 著者 De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL タイトル M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. 雑誌 Nat Genet 11:447-9 (1995) DOI:10.1038/ng1295-447 |