Abstract
Hepatocellular carcinoma (HCC) is diagnosed in more than half a million individuals worldwide every year. It is often invasive and metastatic, resulting in a poor prognosis. Our knowledge of the genomic alterations implicated in HCC initiation and progression is fragmentary, and few molecular alterations unique to HCC are known. We performed whole-exome sequencing for a pleomorphic cell-type HCC tissue and matched normal tissue, and uncovered seven non-synonymous somatic variants in SPATA21, PPCS, CDH12, OR1L3, PCK2, HUWE1 and PHF16. These variants were validated by PCR and sequencing, with the exception of that in PPCS. We further performed a bioinformatics analysis of the six validated variants. The results suggested that the function of the proteins of the three mutated genes, PCK2, HUWE1 and PHF16, may be changed significantly. Among these genes, PCK2, within the insulin signaling pathway, and HUWE1, within the ubiquitin-mediated proteolysis pathway, may be essential for cell proliferation. These pathways are known to be important for hepatocarcinogenesis. Hence, we suggest that PCK2 and HUWE1 are associated with carcinoma cell proliferation in HCC.
Highlights
Hepatocellular carcinoma (HCC) is diagnosed in more than half a million individuals worldwide every year
HCC is understudied compared with other major lethal types of cancer, and our knowledge of the genomic alterations implicated in HCC initiation and progression is fragmentary
We focused our analysis on the six non-synonymous substitutions and one frameshift mutation affecting the integrity of the open reading frame (ORF)
Summary
Hepatocellular carcinoma (HCC) is diagnosed in more than half a million individuals worldwide every year. Rates of liver cancer among males are two to four times as high as the rates among females [1,2,3,4,5]. Despite major efforts to improve the diagnosis and treatment of HCC, therapeutic options remain limited. Especially in Asia and sub-Saharan Africa, present at end stages of the disease or with underlying liver cirrhosis and surgical options may no longer be indicated. HCC is understudied compared with other major lethal types of cancer, and our knowledge of the genomic alterations implicated in HCC initiation and progression is fragmentary. An improved understanding of the molecular genetic alterations specific to HCC may lead to the development of more efficient methods of prevention, early diagnosis and cure of this disease.
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