Background/purpose of the study
Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients.
Methods
Somatic mutation, whole transcriptome, and copy number variations of 36 frozen tissue samples of operably resected HCC tissues by targeted deepsequencing, RNAseq and SNP array.
Results
The samples were classified the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared with the mono-CC tumors. poly-CC HCC is highly proliferative and has a high risk of early recurrence.
Conclusion
CC is a candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.