Open AccessPre‐S2 deletion mutants of hepatitis B virus could have an important role in hepatocarcinogenesis in Asian children
Author(s) -
Abe Kenji,
Thung Swan N.,
Wu HanChieh,
Tran Tung Thanh,
Le Hoang Phuc,
Truong Khai Dinh,
Inui Ayano,
Jang Ja June,
Su IhJen
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01309.x
Subject(s) - hepatocellular carcinoma , hccs , hepatitis b virus , cirrhosis , mutant , carcinogenesis , hepatitis b , virology , hepadnaviridae , biology , medicine , virus , gene , cancer research , gastroenterology , genetics
Although many studies on the risk factors and their carcinogenesis in adult hepatocellular carcinoma (HCC) have been reported, they remain poorly understood in childhood HCC. A retrospective study of 42 HCC cases in Asian children was conducted. Hepatitis B virus (HBV)‐DNA in HCC tissues was detected in 36 of 42 (86%) cases tested, while no hepatitis C virus (HCV)‐RNA was detectable in any of HCCs. Twenty of 36 (56%) HCC cases were accompanied by cirrhosis. Surprisingly, very high prevalence of the HBV pre‐S deletion mutant was recognized in 27 of 30 (90%) HCCs examined. They occurred most frequently in pre‐S2 (20/27, 74%) followed by pre‐S1 (5/27, 18.5%), and both pre‐S1/S2 (2/27, 7.4%). Interestingly, the pre‐S2 mutant consistently appeared with deletion at nt 4‐57 in all of the 20 cases with the pre‐S2 mutant (100%) and within this locus in the two cases with both pre‐S‐1/S2 mutants. Type II ground‐glass hepatocytes in non‐tumorous livers were seen in 15 of the 22 HCCs with the pre‐S2 deletion mutant (68%). This hotspot mutation in the pre‐S2 was further confirmed by complete genomic sequence of HBV in a Japanese boy who eventually developed HCC. Our result strongly suggests that HBV is a major contributor to the development of HCC in Asian children. The HBV pre‐S2 deletion mutant at nt 4‐57 which has a CD8 T‐cell epitope could be responsible for the emergence and aggressive outcome of childhood HCC. Determination of this hotspot mutation in the pre‐S2 region could be a useful index for predicting the clinical outcome of HCC development. ( Cancer Sci 2009; 100: 2249–2254)