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.
(of which Peer Reviewed: 16 results,
Acknowledgement Compliant: 4 results,
Open Access: 2 results)
Ｊｏｕｒｎａｌ ｏｆ Ｈｅｐａｔｏｂｉｌｉａｒｙ Ｐａｎｃｒｅａｔｉｃ Ｓｃｉｅｎｃｅ
Volume: in press
World J Surg.
Journal of Hepato-Billiary-Pancreatic Sciences
World J Surg
Cancer Chemother Pharmacol
Br J Surg
J Surg Res
Proc Natl Acad Sci U S A
Mol Cell Biol
Attribution of KAKENHI