Abstract
Background/purpose of the studyTumor 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.MethodsSomatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array.ResultsThe samples were classified into 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 months 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 to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence.ConclusionCC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.
Highlights
Liver cancer is one of the most common malignancies, with more than 800,000 new cases diagnosed globally each year [1]
The clonal composition of a tumor can be analyzed based on the B-allele frequency (BAF) and log2 ratio (log2R), which can be determined from the whole-genome copy number profiles obtained using the OncoScan FFPE Assay Kit
We previously demonstrated that the whole-genome single nucleotide polymorphism (SNP) array could be applied to the detection of the clonal composition of human ovarian cancer
Summary
Liver cancer is one of the most common malignancies, with more than 800,000 new cases diagnosed globally each year [1]. The OncoScan FFPE Assay Kit (Thermo Fisher Scientific, Wilmington, DE) relies on molecular inversion prove (MIP) technology to detect genome-wide copy number alterations, loss of heterozygosity, and somatic mutation [7]. This assay provides the B-allele frequency (BAF), the log ratio (log2R), and the copy number for each of over 220,000 analyzed polymorphic genomic locations. There is no such limitation in evaluating the BAF in segments with copy number loss, and the clonal composition number can be derived from the presence of aberrant cells with a different BAF pattern
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