The aim of the study was to determine the features of loss of heterozygosity in the mitofusin 2 gene and their association with clinicopathological characteristics of hepatocellular carcinoma.
Methodology
Loss of heterozygosity of four microsatellite loci were detected in tumors and their adjacent normal tissues of 29 surgically resected hepatocellular carcinomas using an ABI3130xl automated sequencer.
Results
The results showed the incidences of loss of heterozygosity on microsatellite loci D1S2667, D1S2740, D1S434, and D1S228 were 21%, 23%, 21%, and 22%, respectively. Loss of heterozygosity in the mitofusin 2 gene was closely correlated with age, degree of differentiation, capsule integrity, and tumor size (P <0.05) but was not correlated with gender, thrombosis, liver cirrhosis, or alpha-fetoprotein levels (P >0.05).
Conclusions
Frequent loss of heterozygosity in the mitofusin 2 gene exists in hepatocellular carcinoma. Loss of heterozygosity, which represents a tumor suppressor gene pathway, may play a critical role in the occurrence and development of hepatocellular carcinoma.
ChenG., LiuN., ZhouA., TangC., MaD., TangJ.: The role of hypertension-related gene in aortic vascular smooth muscle cells from mice and rats. Chin Med J (Engl), 114: 833–836, 2001.
2.
SantelA., FullerM.T.: Control of mitochondrial morphology by a human mitofusin. J Cell Sci, 114: 867–874, 2001.
HofmannW.K., TakeuchiS., XieD., MillerC.W., HoelzerD., KoefflerH.P.: Frequent loss of heterozygosity in the region of D1s450 at 1p36.2 in myelodysplastic syndromes. Leuk Res, 25: 855–858, 2001.
5.
HogartyM.D., MarisJ.M., WhiteP.S., GuoC., BrodeurG.M.: Analysis of genomic imprinting at 1p35–36 in neuroblastoma. Med Pediatr Oncol, 36: 52–55, 2001.
WangW., LuJ., ZhuF., WeiJ., JiaC., ZhangY., ZhouL., XieH., ZhengS.: Pro-apoptotic and anti-proliferative effects of mitofusin-2 via bax signaling in hepatocellular carcinoma cells. Med Oncol, 29: 70–76, 2012.
19.
WangW., ZhouD., WeiJ., WuZ., ChengX., SunQ., XieH., ZhouL., ZhengS.: Hepatitis B virus X protein inhibits p53-mediated upregulation of mitofusin-2 in hepatocellular carcinoma cells. Biochem Biophys Res Commun, 421: 355–360, 2012.
20.
ZhangS.H., CongW.M., XianZ.H., WuM.C.: Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China. World J Gastroenterol, 11: 3034–3039, 2005.
21.
LeungT.H., WongN., LaiP.B., ChanA., ToK.F., LiewC.T., LauW.Y., JohnsonP.J.: Identification of four distinct regions of allelic imbalances on chromosome 1 by the combined comparative genomic hybridization and microsatellite analysis on hepatocellular carcinoma. Mod Pathol, 15: 1213–1220, 2002.
22.
KurokiT., FujiwaraY., TsuchiyaE., NakamoriS., ImaokaS., KanematsuT., NakamuraY.: Accumulation of genetic changes during development and progression of hepatocellular carcinoma: loss of heterozygosity of chromosome arm 1p occurs at an early stage of hepatocarcinogenesis. Genes Chromosomes Cancer, 13: 163–167, 1995.
23.
TanY.J.: Hepatitis B virus infection and the risk of hepatocellular carcinoma. World J Gastroenterol, 17: 4853–4857, 2011.
