MOUNTAIN VIEW, Calif., Feb. 23, 2012 (GLOBE NEWSWIRE) -- Complete Genomics Inc. (Nasdaq:GNOM) announced today that Genome Research has published a paper it co-authored describing the effects of hepatitis B virus (HBV) integration into the genomes of liver cancer patients. HBV infection is a recognized risk factor for the development of liver cancer. The paper, co-authored with researchers at a leading biotechnology company, is available online at http://genome.cshlp.org/content/early/2012/01/20/gr.133926.111.abstract.
Complete Genomics sequenced the tumor and matching non-tumor genomes for four liver cancer patients; three of the patients were HBV positive and one was HBV negative. In addition to performing its standard analyses for somatic small variations, copy number variations and structural variations, Complete Genomics also identified the specific strains of virus infecting the HBV positive patients. It then used its structural variation detection capabilities to discover viral incorporation sites in the human genome. This paper represents the most comprehensive characterization to date of HBV integration in liver cells. The paper demonstrates an increased mutagenic load induced by HBV infection through an integrated analysis of genomic sequence data with other data sources, such as RNA sequencing.
"We believe this study demonstrates that Complete Genomics' data and core methodology can be used to accurately identify viral incorporation sites, including insertions present in only a small proportion of the sequenced cells and that might be missed by using other methods like exome sequencing," said Dr. Clifford Reid, chairman, president and CEO of Complete Genomics.
Dr. Dennis Ballinger, the company's vice president of genomics, added, "There is a known increased rate of liver cancer in individuals infected with HBV. The paper suggests that this increased prevalence is due in part to an increased mutagenic load induced by HBV insertion into genomic DNA. These insertion events often alter the function of one or more adjacent genes, as seen from a co-analysis of genomic sequence with other data types."
Sequencing at Complete Genomics' high coverage level (>80x) enabled the detection of rare integration events that, when combined with transcriptome sequencing from another technology, permitted an investigation of the transcriptional impact of viral insertions. In one patient, both the tumor and the normal samples were sequenced at ultra-high depth (234x coverage), resulting in the detection of a large number of low-frequency viral insertion events across the genome. The resulting genomic data also revealed differences between viral incorporation patterns in tumor and non-tumor liver tissue. In non-tumor liver tissue, a heterogeneous collection of insertion-containing liver cells was discovered, with each represented in a low fraction of the sample. In addition, a small subset of insertion sites (nine in all) in the HBV-positive tumor samples appeared to be present in a large proportion of the tumor cells, likely the result of clonal expansion that occurred early in the cancer's development.
The authors also analyzed the mutation spectrum of these liver cancer patients in considerable detail, observing that the mutation signature in liver cancer was distinct from earlier studies of tobacco smoking1,2 and UV damage3. The dominant substitutions observed were A>G and C>T transition events.
In addition, several structural variations were detected and confirmed in the liver cancer tumors, including a fusion event between AXIN1 and LUC7L genes in one patient that resulted in a truncated AXIN1 and up-regulation of LUC7L. Overall, 51 structural variations were detected overlapping RefSeq genes, of which 37 (70%) were successfully confirmed at single-base resolution using polymerase chain reaction and sequencing.
References
- Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, Stinson J, Yue P, Zhang Y, Pant KP, Bhatt D et al. 2010. The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465(7297): 473-477.
- Pleasance ED, Stephens PJ, O'Meara S, McBride DJ, Meynert A, Jones D, Lin M-L, Beare D, Lau KW, Greenman C et al. 2010b. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463(7278): 184-190.
- Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, Varela I, Lin M-L, Ordóñez GR, Bignell GR et al. 2010a. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463(7278): 191-196.
About Complete Genomics
Complete Genomics is the whole human genome sequencing company that has developed and commercialized an innovative DNA sequencing service. The Complete Genomics Analysis Platform (CGA™ Platform) combines Complete Genomics' proprietary human genome sequencing technology with advanced informatics and data management software. Additional information can be found at http://www.completegenomics.com.
The Complete Genomics logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=8216
Forward-looking Statements
Certain statements in this press release, including statements relating to whether researchers will be able to use Complete Genomics' data and core methodology to accurately identify viral incorporation sites, including insertions that are present in only a small proportion of the sequenced cells and might be missed by using other methods, are forward-looking statements that are subject to risks and uncertainties. Readers are cautioned that these forward-looking statements are based on management's current expectations, and actual results may differ materially from those projected. The following factors, without limitation, could cause actual results to differ materially from those in the forward-looking statements: the ability of scientists to successfully analyze the genomic data we provide, the ability of researchers to convert genomic data into medically valuable information, and contamination of DNA samples or other failures in the sequencing process. More information on potential factors that could affect risks related to Complete Genomics' sequencing process and the Company's financial and operational results can be found in its Annual Report on Form 10-K filed on March 30, 2011 and its Quarterly Reports on Form 10-Q, including those listed under the caption "Risk Factors." The Company disclaims any obligation to update information contained in these forward-looking statements, whether as a result of new information, future events or otherwise.