کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2042507 | 1073200 | 2015 | 19 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Circulating Tumor DNA Analysis for Liver Cancers and Its Usefulness as a Liquid Biopsy Circulating Tumor DNA Analysis for Liver Cancers and Its Usefulness as a Liquid Biopsy](/preview/png/2042507.png)
Background & AimsCirculating tumor DNA (ctDNA) carrying tumor-specific sequence alterations has been found in the cell-free fraction of blood. Liver cancer tumor specimens are difficult to obtain, and noninvasive methods are required to assess cancer progression and characterize underlying genomic features.MethodsWe analyzed 46 patients with hepatocellular carcinoma who underwent hepatectomy or liver transplantation and for whom whole-genome sequencing data was available. We designed personalized assays targeting somatic rearrangements of each tumor to quantify serum ctDNA. Exome sequencing was performed using cell-free DNA paired primary tumor tissue DNA from a patient with recurrent liver cancer after transcatheter arterial chemoembolization (TACE).ResultsWe successfully detected ctDNA from 100 μL of serum samples in 7 of the 46 patients before surgery, increasing with disease progression. The cumulative incidence of recurrence and extrahepatic metastasis in the ctDNA-positive group were statistically significantly worse than in the ctDNA-negative group (P = .0102 and .0386, respectively). Multivariate analysis identified ctDNA (OR 6.10; 95% CI, 1.11–33.33, P = .038) as an independent predictor of microscopic vascular invasion of the portal vein (VP). We identified 45 nonsynonymous somatic mutations in cell-free DNA after TACE and 71 nonsynonymous somatic mutations in primary tumor tissue by exome sequencing. We identified 25 common mutations in both samples, and 83% of mutations identified in the primary tumor could be detected in the cell-free DNA.ConclusionsThe presence of ctDNA reflects tumor progression, and detection of ctDNA can predict VP and recurrence, especially extrahepatic metastasis within 2 years. Our study demonstrated the usefulness of ctDNA detection and sequencing analysis of cell-free DNA for personalized treatment of liver cancer.
Journal: CMGH Cellular and Molecular Gastroenterology and Hepatology - Volume 1, Issue 5, September 2015, Pages 516–534