Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease
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 a...
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2021
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oai:doaj.org-article:b208dfd6ee5e4b9ea59f6d6721684d8a2021-11-25T17:13:22ZAccumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease10.3390/cells101132572073-4409https://doaj.org/article/b208dfd6ee5e4b9ea59f6d6721684d8a2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3257https://doaj.org/toc/2073-4409The 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 (<i>n</i> = 8), and those with grade 1 or lower were classified as the non-fibrosis progression group (<i>n</i> = 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.Satoru HagiwaraNaoshi NishidaKazuomi UeshimaYasunori MinamiYoriaki KomedaTomoko AokiMasahiro TakitaMasahiro MoritaHirokazu ChishinaAkihiro YoshidaHiroshi IdaMasatoshi KudoMDPI AGarticlegenomeliver cancermutationnon-alcoholic fatty liver diseasemethylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3257, p 3257 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
genome liver cancer mutation non-alcoholic fatty liver disease methylation Biology (General) QH301-705.5 |
| spellingShingle |
genome liver cancer mutation non-alcoholic fatty liver disease methylation Biology (General) QH301-705.5 Satoru Hagiwara Naoshi Nishida Kazuomi Ueshima Yasunori Minami Yoriaki Komeda Tomoko Aoki Masahiro Takita Masahiro Morita Hirokazu Chishina Akihiro Yoshida Hiroshi Ida Masatoshi Kudo Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease |
| description |
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 (<i>n</i> = 8), and those with grade 1 or lower were classified as the non-fibrosis progression group (<i>n</i> = 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. |
| format |
article |
| author |
Satoru Hagiwara Naoshi Nishida Kazuomi Ueshima Yasunori Minami Yoriaki Komeda Tomoko Aoki Masahiro Takita Masahiro Morita Hirokazu Chishina Akihiro Yoshida Hiroshi Ida Masatoshi Kudo |
| author_facet |
Satoru Hagiwara Naoshi Nishida Kazuomi Ueshima Yasunori Minami Yoriaki Komeda Tomoko Aoki Masahiro Takita Masahiro Morita Hirokazu Chishina Akihiro Yoshida Hiroshi Ida Masatoshi Kudo |
| author_sort |
Satoru Hagiwara |
| title |
Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease |
| title_short |
Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease |
| title_full |
Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease |
| title_fullStr |
Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease |
| title_full_unstemmed |
Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease |
| title_sort |
accumulation of genetic and epigenetic alterations in the background liver and emergence of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/b208dfd6ee5e4b9ea59f6d6721684d8a |
| work_keys_str_mv |
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| _version_ |
1718412612443570176 |