AIMS: To investigate the clonality and chromosome abnormalities of nodules of altered hepatocytes (NAH) in liver cirrhosis and determine whether there is a genetic link between monoclonal NAH and hepatocellular carcinoma (HCC). METHODS AND RESULTS: First, 93 nodules from nine hepatitis B virus (HBV)-related liver cirrhosis patients were dissected by laser microdissection. Next, genomic DNA was extracted, pretreated with Hpa II or Hha I, and amplified via nested polymerase chain reaction for the phosphoglycerate kinase and androgen receptor genes. Finally, the chromosomal aberrations of 12 monoclonal NAH were studied using array-based comparative genomic hybridization (array-CGH). Loss of X chromosomal inactivation mosaicism was demonstrated in three large regenerative nodules and 12 NAH with small cell change (SCC), indicating their neoplastic nature. Among the 60 NAH without SCC, 29 (48.33%) were shown to be monoclonal, whereas four glycogen-storing foci and 14 regenerative nodules were found to be polyclonal. Array-CGH analysis revealed chromosomal abnormalities in one NAH with SCC. Moreover, a part of chromosomal abnormalities in the NAH with SCC coincided with those in HCC. CONCLUSIONS: Some (48.33%) NAH in HBV-associated cirrhosis, particularly all those with SCC, are already neoplastic lesions. Occurrence of SCC is a late event during NAH progression, suggesting a premalignant phenotype.
AIMS: To investigate the clonality and chromosome abnormalities of nodules of altered hepatocytes (NAH) in liver cirrhosis and determine whether there is a genetic link between monoclonal NAH and hepatocellular carcinoma (HCC). METHODS AND RESULTS: First, 93 nodules from nine hepatitis B virus (HBV)-related liver cirrhosispatients were dissected by laser microdissection. Next, genomic DNA was extracted, pretreated with Hpa II or Hha I, and amplified via nested polymerase chain reaction for the phosphoglycerate kinase and androgen receptor genes. Finally, the chromosomal aberrations of 12 monoclonal NAH were studied using array-based comparative genomic hybridization (array-CGH). Loss of X chromosomal inactivation mosaicism was demonstrated in three large regenerative nodules and 12 NAH with small cell change (SCC), indicating their neoplastic nature. Among the 60 NAH without SCC, 29 (48.33%) were shown to be monoclonal, whereas four glycogen-storing foci and 14 regenerative nodules were found to be polyclonal. Array-CGH analysis revealed chromosomal abnormalities in one NAH with SCC. Moreover, a part of chromosomal abnormalities in the NAH with SCC coincided with those in HCC. CONCLUSIONS: Some (48.33%) NAH in HBV-associated cirrhosis, particularly all those with SCC, are already neoplastic lesions. Occurrence of SCC is a late event during NAH progression, suggesting a premalignant phenotype.
Authors: Min Zhu; Tianshi Lu; Yuemeng Jia; Xin Luo; Purva Gopal; Lin Li; Mobolaji Odewole; Veronica Renteria; Amit G Singal; Younghoon Jang; Kai Ge; Sam C Wang; Mahsa Sorouri; Justin R Parekh; Malcolm P MacConmara; Adam C Yopp; Tao Wang; Hao Zhu Journal: Cell Date: 2019-04-04 Impact factor: 41.582