July 1, 2013, Shenzhen, China - The Asian Cancer Research Group (ACRG), an independent, not-for-profit company in collaboration with BGI, the world's largest genomics organization, and The University of Hong Kong (HKU), jointly announced the publication of findings from a study of recurrent mutations in hepatocellular carcinoma (HCC), one of the most deadly cancers worldwide, in the international journal Genome Research. The study provides new insights into potential therapeutic intervention strategies for this common form of liver cancer.
HCC is a primary malignancy of the hepatocytes, generally leading to death within 6-20 months after diagnosis. This type of cancer is more common in parts of Africa and Asia, where the patients with hepatitis B or C are at risk for liver cancer, even if they have not developed cirrhosis. HCC has limited treatment options such as surgical resection of the tumor at its early stage, and the molecular basis of its occurrence and development remains poorly understood.
In this study, researchers used whole genome sequencing (WGS) to survey a cohort of 88 matched HCC tumor and normal samples from Hong Kong for investigating alerted genes and the pathways implicated in HBV-associated HCC. They found that TP53 was the most commonly mutated tumor suppressor gene, accounting for 35.2% in the HCC cohort. Generally, the patients with tumors containing TP53 mutations exhibited poor survival.
The Wnt/β-Catenin signaling pathway is central for liver functions and is frequently abnormal activated in the carcinogenesis of HCC. Researchers in this study found β-catenin maybe the most frequently mutated oncogene. In addition to β-catenin, they found relative high mutation rates in genes in the JAK/STAT pathway, which may act as a major oncogenic driver in HCC tumor progression.
Hancheng Zheng, group leader of this project at BGI, said, "Liver cancer is intractable to nearly all currently available anti-cancer targeted therapies. Our findings in this study provide a better understanding of molecular basis of hepatocarcinogenesis and provide new clues to improving the diagnosis and treatment of liver cancer in the future."
"We detected a series of genes and pathways implicated in HBV-associated HCC using whole genome sequencing, which contribute to a better understanding of the tumor biology and targeted drug screening," said Dr. James Hardwick, Vice President of ACRG, and Director of Informatics & Analysis at Merck, "The ACRG was established to fuel research directed towards improving our understanding of cancers affecting Asian populations. By working together, we are able to generate important breakthroughs that can be transformed to better fight against liver cancer in the future."
"As clinicians, we are very excited about the several prevalent and actionable mutations identified from the study, including activating mutations of JAK1, which warrant testing several existing inhibitors for the treatment of the disease preclinically and clinically," said Dr. Ronnie Poon, Chair Professor and Chief, Division of Hepatobiliary and Pancreatic Surgery, The University of Hong Kong.
About the Asian Cancer Research Group, Inc. (ACRG)
Formed in 2010, ACRG is an independent, not-for-profit company established jointly by Eli Lilly and Company, MSD (known as Merck in the United States and Canada), and Pfizer Inc. to accelerate research and ultimately improve treatment for patients affected with the most commonly-diagnosed cancers in Asia. The goal of ACRG is to improve the knowledge of cancers prevalent in Asia by freely sharing data generated by the ACRG with the scientific community in order to accelerate drug discovery efforts. This collaboration exemplifies a model in which large pharmaceutical companies combine their resources and expertise to more rapidly increase knowledge in the scientific community of underserved diseases with the hope of enabling the discovery of more effective therapies for patients. ACRG is focusing its initial efforts on Asian liver, gastric and lung cancers.
BGI was founded in Beijing, China, in 1999 with the mission to become a premier scientific partner for the global research community. The goal of BGI is to make leading-edge genomic science highly accessible, which it achieves through its investment in infrastructure, leveraging the best available technology, economies of scale, and expert bioinformatics resources. BGI, and its affiliates, BGI Americas, headquartered in Cambridge, MA, and BGI Europe, headquartered in Copenhagen, Denmark, have established partnerships and collaborations with leading academic and government research institutions as well as global biotechnology and pharmaceutical companies, supporting a variety of disease, agricultural, environmental, and related applications.
BGI has a proven track record of excellence, delivering results with high efficiency and accuracy for innovative, high-profile research: research that has generated over 200 publications in top-tier journals such as Nature and Science. BGI's many accomplishments include: sequencing one percent of the human genome for the International Human Genome Project, contributing 10 percent to the International Human HapMap Project, carrying out research to combat SARS and German deadly E. coli, playing a key role in the Sino-British Chicken Genome Project, and completing the sequence of the rice genome, the silkworm genome, the first Asian diploid genome, the potato genome, and, more recently, have sequenced the human Gut Metagenome, and a significant proportion of the genomes for the1000 Genomes Project. For more information about BGI, please visit http://www.genomics.cn.
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