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Genomic Portrait of Resectable Hepatocellular Carcinomas: Implications of RB1 and FGF19 Aberrations for Patient Stratification

Title
Genomic Portrait of Resectable Hepatocellular Carcinomas: Implications of RB1 and FGF19 Aberrations for Patient Stratification
Author
공구
Keywords
HELICOBACTER-PYLORI INFECTION; CHOLESTEROL GALLSTONE FORMATION; INDUCED GASTRIC PATHOLOGY; MULTIPLEX SEROLOGY; CHRONIC CHOLECYSTITIS; ATROPHIC GASTRITIS; BILIARY-TRACT; C57BL/6 MICE; CANCER RISK; HUMAN LIVER
Issue Date
2014-09
Publisher
WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Citation
HEPATOLOGY, 2014, 60(6), P.1972-1982
Abstract
Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P50.038 and P50.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P50.017). Conclusion: RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients.
URI
http://onlinelibrary.wiley.com/doi/10.1002/hep.27198/abstract;jsessionid=8DA9197EAE2EF0E9E011599FA4779480.f03t03?systemMessage=Wiley+Online+Library+is+migrating+to+a+new+platform+powered+by+Atypon%2C+the+leading+provider+of+scholarly+publishing+platforms.+The+new+Wiley+Online+Library+will+be+migrated+over+the+weekend+of+March+17+and+18.You+should+not+experience+any+issues+or+loss+of+access+during+this+time.+For+more+information%2C+please+visit+our+migration+page%3A++http%3A%2F%2Fwww.wileyactual.com%2FWOLMigration%2Fhttp://hdl.handle.net/20.500.11754/48366
ISSN
0270-9139; 1527-3350
DOI
10.1002/hep.27198
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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