Yasushi Totoki,1 Kenji Tatsuno,2 Shogo Yamamoto,2 Yasuhito Arai,1 Fumie Hosoda,1 Shumpei Ishikawa,3 Shuichi Tsutsumi,2 Kohtaro Sonoda,2 Hirohiko Totsuka,4 Takuya Shirakihara,1 Hiromi Sakamoto,4 Linghua Wang,2 Hidenori Ojima,5 Kazuaki Shimada,6 Tomoo Kosuge,6 Takuji Okusaka,7 Kazuto Kato,8 Jun Kusuda,9 Teruhiko Yoshida,4 Hiroyuki Aburatani2 & Tatsuhiro Shibata1
Affiliations
Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Yasushi Totoki,Yasuhito Arai,Fumie Hosoda,Takuya Shirakihara &Tatsuhiro Shibata
Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Meguro-ku, Tokyo, Japan.
Kenji Tatsuno,Shogo Yamamoto,Shuichi Tsutsumi,Kohtaro Sonoda,Linghua Wang &Hiroyuki Aburatani
Department of Pathology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Shumpei Ishikawa
Division of Genetics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Hirohiko Totsuka,Hiromi Sakamoto &Teruhiko Yoshida
Division of Molecular Pathology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Hidenori Ojima
Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Kazuaki Shimada &Tomoo Kosuge
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Takuji Okusaka
Institute for Research in Humanities, Graduate School of Biostudies, Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan.
Kazuto Kato
National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
Jun Kusuda
Contributions
The study was designed by T. Shibata, H.A., T.Y. and J.K. Sequencing and data analyses were conducted by Y.T., K.T., S.Y., S.T., K. Sonoda and H.T. Allele typing and copy number analyses were performed by H.S. and S.I. Other molecular studies were done by Y.A., F.H., T. Shirakihara, and L.W.; H.O., K. Shimada, T.K., T.O. and K.K. coordinated collection of clinical sample and information. The manuscript was written by Y.T., T. Shibata, K.T., S.Y., H.A. and T.Y.
Competing financial interests
The authors declare no competing financial interests.
Corresponding author
Correspondence to: Tatsuhiro Shibata
Journal name: Nature Genetics
Year published:(2011)
DOI: doi:10.1038/ng.804
Received24 November 2010
Accepted14 March 2011
Published online17 April 2011
Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide1. By massively parallel sequencing2 of a primary hepatitis C virus–positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis3 of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing4, 5 at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.
Figures at a glance
Figure 1: Somatic substitution pattern of the liver cancer genome.
High-resolution characterization of a hepatocellular carcinoma genome : Nature Genetics : Nature Publishing Group
HEPATOLOGÍA
Nuevos datos sobre la relación genética entre el virus de la hepatitis C y el carcinoma hepatocelular
JANO.es y agencias · 18 Abril 2011 12:43
.Dos estudios publicados por investigadores japoneses han permitido identificar mutaciones específicas.
Virus de la hepatitis C.
Dos estudios publicados en la edición digital de Nature Genetics avanzan en el conocimiento de los vínculos genéticos que existen entre cáncer de hígado y la infección por el virus de la hepatitis C. Más de 170 millones de personas en todo el mundo están infectadas con el virus de la hepatitis C, principal factor de riesgo de la cirrosis hepática y el carcinoma hepatocelular.
Los científicos presentan el genoma de un carcinoma hepatocelular positivo para el virus de la hepatitis C (VHC), así como una localización de riesgo genético para el carcinoma hepatocelular (HCC) inducido por el VHC.
El equipo de Tatsuhiro Shibata, del Instituto de Investigación del Centro Nacional del Cáncer en Tokio, secuenció un tumor de carcinoma hepatocelular positivo para el virus de la hepatitis C y lo confrontó con células normales de un varón japonés. Los científicos identificaron miles de mutaciones específicas del tumor.
Por otro lado, investigadores de la Universidad de Tokio dirigidos por Koichi Matsuda, realizaron un análisis amplio de genoma de 1.394 individuos de ancestros japoneses con carcinoma hepatocelular inducido por el virus de la hepatitis C. Los autores identificaron una localización en el cromosoma 6p21 que está fuertemente asociada al carcinoma hepatocelular inducido por el VHC.
Nature Genetics 2011; doi:10.1038/ng.804
High-resolution characterization of a hepatocellular carcinoma genome : Nature Genetics : Nature Publishing Group
Nature Genetics 2011;doi:10.1038/ng.809
Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma : Nature Genetics : Nature Publishing Group
Nature Genetics
Home : Nature Genetics
University of Tokyo
The University of Tokyo.
Actualidad Ultimas noticias - JANOes y agencias - Nuevos datos sobre la relacion genetica entre el virus de la hepatitis C y el carcinoma hepatocelular - JANO.es - ELSEVIER
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