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- Title
Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease.
- Authors
Hagiwara, Satoru; Nishida, Naoshi; Ueshima, Kazuomi; Minami, Yasunori; Komeda, Yoriaki; Aoki, Tomoko; Takita, Masahiro; Morita, Masahiro; Chishina, Hirokazu; Yoshida, Akihiro; Ida, Hiroshi; Kudo, Masatoshi
- Abstract
The incidence of hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We analyzed 16 surgically resected HCC cases in which the background liver was pathologically diagnosed as NAFLD. Specimens with Brunt classification grade 3 or higher were assigned as the fibrotic progression group (n = 8), and those with grade 1 or lower were classified as the non-fibrosis progression group (n = 8). Comprehensive mutational and methylome analysis was performed in cancerous and noncancerous tissues. The target gene mutation analysis with deep sequencing revealed that CTNNB1 and TP53 mutation was observed in 37.5% and TERT promoter mutation was detected in 50% of cancerous samples. Furthermore, somatic mutations in non-cancerous samples were less frequent, but were observed regardless of the progression of fibrosis. Similarly, on cluster analysis of methylome data, status for methylation events involving non-cancerous liver was similar regardless of the progression of fibrosis. It was found that, even in cases of non-progressive fibrosis, accumulation of gene mutations and abnormal methylation within non-cancerous areas were observed. Patients with NAFLD require a rigorous liver cancer surveillance due to the high risk of HCC emergence based on the accumulation of genetic and epigenetic abnormalities, even when fibrosis is not advanced.
- Subjects
NON-alcoholic fatty liver disease; HEPATOCELLULAR carcinoma; EPIGENETICS; LIVER cancer; LIVER; LIVER cells
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 11, p3257
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10113257