Deep sequencing analysis of cancer-related genes in early hepatocellular carcinoma in the livers with and without hepatitis virus

<Background>It became apparent that hepatocellular carcinoma (HCC) still develops in a substantial number of patients even after the introduction of recently-advanced anti-HBV and anti-HCV therapies, and the reason is not clear.
<Methods>Twelve early solitary HCCs with different etiologies (3 HBV, 3 HCV, 3 HCV-SVR and 3 NBNC) were included. After precise collection of tumor tissues from FFPE samples by laser-captured microdissection, deep sequencing of cancer-related genes was performed targeting 50 genes with 2800 hot-spots.
<Results >4,287 reads (average) were obtained in each hot-spot. Significant HCC-related hot-spot mutations were only observed in CTNNB1 (33%, 4/12) and TP53 (33%, 4/12). TP53 mutation was observed only in HCV-related HCCs {4/6 (66%) in HCV/HCV-SVR vs. 0/6(0%) in HBV/NBNC, p=0.06}. Copy number variation (CNV) was observed in 7/12 (58%) of HCCs and was significantly more frequent in those with hot spot mutations (p<0.001). CNV was less frequent significantly in NBNC-HCCs (p<0.05). Patients were divided into two groups with high mutations/high CNVs (n=7) and with low mutations/low CNVs (n=5). Those with low mutations low CNVs showed high G-GTP (p<0.05), tended to have diabetes (p=0.2) and F4 (p=0.1).
<Conclusions>According to mutation/CNV profiles, early HCCs were separated into two groups, and those two groups might show different clinical characteristics indicating the importance of these analyses.