Research Project
Grant-in-Aid for Scientific Research (A)
Early hepatocellular carcinoma (HCC) is histologically diagnosed as the existence of intratumoral portal tracts and develops into classical HCC. To identify sequential genomic changes in stepwise hepatocarcinogenesis, we analyzed 47 early and 105 classical HCCs using next generation sequencer. Mutations in p53/RB and WNT pathways were recurrently observed both in early and classical HCCs. Exome and RNA sequences frequently showed mutation of promoter region and increased expression of TERT. On the other hand, inactivation in SWI/SNF complexes were observed more often in classical HCC (23.8%) than early HCC (8.5%, P=0.027), and mTOR/PI3K pathway was aberrantly activated in classical HCC (8.5% vs 29.5%, P=0.003) by integrated analysis. Taken together, inactivating mutations of p53/RB and WNT signaling pathways and TERT up-regulation are the first events in hepatocarcinogenesis and aberrations of SWI/SNF complexes and mTOR/PI3K pathway may play pivotal roles in the progression of HCC.
All 2015 2014 2013 2012
All Journal Article (16 results) (of which Peer Reviewed: 16 results, Acknowledgement Compliant: 4 results, Open Access: 2 results) Presentation (7 results) Book (6 results)
Journal of Hepatobiliary Pancreatic Science
Volume: in press
10.1002/jhbp.101
World J Surg.
Volume: 39 Pages: 471-477
10.1007/s00268-014-2828-0
Hepatology
Volume: 61(2) Pages: 437-446
10.1002/hep.27426
Nature Genetics
Volume: 46 Pages: 1267-1273
10.1038/ng.3126
Cancer Med
Volume: 3 Pages: 1235-45
10.1002/cam4.273
Journal of Hepato-Billiary-Pancreatic Sciences
Volume: 21
10.1002/jhbp.93
Surg Today
Volume: 43 Pages: 865-870
10.1007/s00595-012-0308-4
10031189765
World J Surg
Volume: 37 Pages: 487-453
10.1007/s00268-012-1887-3
Cancer Chemother Pharmacol
Volume: 71 Pages: 727-731
10.1007/s00280-012-2066-9
J Hepatol
Volume: 58 Pages: 306-11
10.1016/j.jhep.2012.09.026
Br J Surg
Volume: 99 Pages: 1584-90
10.1002/bjs.8916
J Surg Res
Volume: 172 Pages: 133-8
10.1016/j.jss.2012.01.003
Proc Natl Acad Sci U S A
Volume: 109 Pages: 20584-20589
10.1073/pnas.1208651109
EMBO J
Volume: 31 Pages: 4404-14
10.1038/emboj.2012.288
J Neurosci
Volume: 32 Pages: 12543-57
Mol Cell Biol
Volume: Aug;32(15) Pages: 3018-3032
10.1128/mcb.06643-11