Sporadic PCDH18 somatic mutations in EpCAM-positive hepatocellular carcinoma
Abstract
The relationship between specific genome alterations and hepatocellular carcinoma (HCC) cancer stem cells (CSCs) remains unclear. In this study, we evaluated the relationship between somatic mutations and epithelial cell adhesion molecule positive (EpCAM(+)) CSCs. Two patient-derived HCC samples (HCC1 and HCC2) were sorted by EpCAM expression and analyzed by whole exome sequence. We measured PCDH18 expression level in eight HCC cell lines as well as HCC1 and HCC2 by real-time quantitative RT-PCR. We validated the identified gene mutations in 57 paired of HCC and matched non-cancerous liver tissues by Sanger sequence. Whole exome sequencing on the sorted EpCAM(+) and EpCAM(-) HCC1 and HCC2 cells revealed 19,263 nonsynonymous mutations in the cording region. We selected mutations that potentially impair the function of the encoded protein. Ultimately, 60 mutations including 13 novel nonsense and frameshift mutations were identified. Among them, PCDH18 mutation was more frequently detected in sorted EpCAM(+) cells than in EpCAM(-) cells in HCC1 by whole exome sequences. However, we could not confirm the difference of PCDH18 mutation frequency between sorted EpCAM(+) and EpCAM(-) cells by Sanger sequencing, indicating that PCDH18 m...Continue Reading
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EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma
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Carcinoma, Hepatocellular
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