Building a Comprehensive Genomic Program for Hepatocellular Carcinoma
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Hepatocellular carcinoma (HCC) is the most common primary liver cancer, causing approximately 660,000 deaths worldwide annually. The preferred treatment of HCC is surgical resection or orthotopic liver transplantation (OLT) for patients meeting specific criteria. For patients outside these criteria, options are limited and include medical therapy, radiofrequency ablation, chemoembolization, or palliative measures, and these result in poor outcomes. Various centers at Baylor are elucidating the genomics of HCC to improve treatment options, with a focus on three etiologies: hepatitis C virus, hepatitis B virus, and non-viral.
Through collaborative efforts, we have established an effective specimen biobanking protocol, and we are using several techniques to analyze HCC, including whole genome sequencing, whole exome sequencing, gene-specific analysis, gene expression, and epigenetic analysis.
We have completed whole genome sequencing on two patient samples, whole exome sequencing on 47 patient samples, gene-specific analysis on 94 patient samples, gene expression on 4 patient samples, and epigenetic analysis on 1 patient sample.
We hope to use these results to define novel genetic therapeutic strategies that may work in conjunction with surgical approaches to improve long-term patient and graft survival rates in patients with HCC. We also aim to provide a functional framework of a comprehensive program for genomic analysis that may be imitated by other institutions and for other tumors in the global quest toward personalized genomic medicine.
KeywordsOrthotopic Liver Transplantation Exome Sequencing Milan Criterion Epigenetic Analysis Illumina Solexa Sequencer
This work was presented at the Molecular Surgeon Symposium on Personalized Genomic Medicine and Surgery–Development of Clinical Model of Genomic Studies at the Baylor College of Medicine, Houston, Texas, May 7, 2010. The authors are grateful to the personnel at the Human Genome Sequencing Center at Baylor College of Medicine. Special acknowledgement also goes to the surgical team of The Liver Center at Baylor College of Medicine, and the residents from the Michael E. DeBakey Department of Surgery. This study was supported in part by grants from National Institutes of Health (NIH) U54-HG003273; U54-HG004973 (to R.A.G.), Cancer Prevention & Research Institution of Texas (CPRIT) grant RP101353-P01/P07 (also to R.A.G.).
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