Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer

Akihiro Fujimoto¹, Mayuko Furuta¹, Yasushi Totoki², Tatsuhiko Tsunoda^{3

4

5}, Mamoru Kato^{5

6}, Yuichi Shiraishi⁷, Hiroko Tanaka⁷, Hiroaki Taniguchi¹, Yoshiiku Kawakami⁸, Masaki Ueno⁹, Kunihito Gotoh¹⁰, Shun-Ichi Ariizumi¹¹, Christopher P Wardell¹, Shinya Hayami⁹, Toru Nakamura¹², Hiroshi Aikata⁸, Koji Arihiro¹³, Keith A Boroevich³, Tetsuo Abe³, Kaoru Nakano¹, Kazuhiro Maejima¹, Aya Sasaki-Oku¹, Ayako Ohsawa¹, Tetsuo Shibuya¹⁴, Hiromi Nakamura², Natsuko Hama², Fumie Hosoda², Yasuhito Arai², Shoko Ohashi², Tomoko Urushidate¹⁵, Genta Nagae¹⁶, Shogo Yamamoto¹⁶, Hiroki Ueda¹⁶, Kenji Tatsuno¹⁶, Hidenori Ojima¹⁷, Nobuyoshi Hiraoka¹⁸, Takuji Okusaka¹⁹, Michiaki Kubo²⁰, Shigeru Marubashi¹⁰, Terumasa Yamada¹⁰, Satoshi Hirano¹², Masakazu Yamamoto¹¹, Hideki Ohdan²¹, Kazuaki Shimada²², Osamu Ishikawa¹⁰, Hiroki Yamaue⁹, Kazuki Chayama^{8

23}, Satoru Miyano^{7

14}, Hiroyuki Aburatani¹⁶, Tatsuhiro Shibata^{2

15}, Hidewaki Nakagawa¹

Affiliations

¹ Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
² Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
³ Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁴ Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵ CREST, JST, Tokyo, Japan.
⁶ Department of Bioinformatics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
⁷ Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁸ Department of Medicine and Molecular Science, Hiroshima University School of Medicine, Hiroshima, Japan.
⁹ Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
¹⁰ Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
¹¹ Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
¹² Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
¹³ Department of Anatomical Pathology, Hiroshima University School of Medicine, Hiroshima, Japan.
¹⁴ Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁵ Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁶ Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
¹⁷ Department of Pathology, Keio University School of Medicine, Shinjyuku-ku, Tokyo, Japan.
¹⁸ Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
¹⁹ Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
²⁰ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
²¹ Department of Gastroenterological Surgery, Hiroshima University School of Medicine, Hiroshima, Japan.
²² Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
²³ Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan.

PMID: 27064257
DOI: 10.1038/ng.3547

Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer

Akihiro Fujimoto et al. Nat Genet. 2016 May.

. 2016 May;48(5):500-9.

doi: 10.1038/ng.3547. Epub 2016 Apr 11.

Authors

Affiliations

¹ Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
² Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
³ Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁴ Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵ CREST, JST, Tokyo, Japan.
⁶ Department of Bioinformatics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
⁷ Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁸ Department of Medicine and Molecular Science, Hiroshima University School of Medicine, Hiroshima, Japan.
⁹ Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
¹⁰ Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
¹¹ Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
¹² Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
¹³ Department of Anatomical Pathology, Hiroshima University School of Medicine, Hiroshima, Japan.
¹⁴ Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁵ Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁶ Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
¹⁷ Department of Pathology, Keio University School of Medicine, Shinjyuku-ku, Tokyo, Japan.
¹⁸ Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
¹⁹ Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
²⁰ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
²¹ Department of Gastroenterological Surgery, Hiroshima University School of Medicine, Hiroshima, Japan.
²² Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
²³ Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan.

PMID: 27064257
DOI: 10.1038/ng.3547

Erratum in

Erratum: Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer.
Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, Tanaka H, Taniguchi H, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Wardell CP, Hayami S, Nakamura T, Aikata H, Arihiro K, Boroevich KA, Abe T, Nakano K, Maejima K, Sasaki-Oku A, Ohsawa A, Shibuya T, Nakamura H, Hama N, Hosoda F, Arai Y, Ohashi S, Urushidate T, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Ojima H, Hiraoka N, Okusaka T, Kubo M, Marubashi S, Yamada T, Hirano S, Yamamoto M, Ohdan H, Shimada K, Ishikawa O, Yamaue H, Chayama K, Miyano S, Aburatani H, Shibata T, Nakagawa H. Fujimoto A, et al. Nat Genet. 2016 May 27;48(6):700. doi: 10.1038/ng0616-700a. Nat Genet. 2016. PMID: 27230686 No abstract available.

Abstract

Liver cancer, which is most often associated with virus infection, is prevalent worldwide, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 liver cancers from Japanese individuals. Our comprehensive analysis identified point mutations, structural variations (STVs), and virus integrations, in noncoding and coding regions. We discovered mutational signatures related to liver carcinogenesis and recurrently mutated coding and noncoding regions, such as long intergenic noncoding RNA genes (NEAT1 and MALAT1), promoters, CTCF-binding sites, and regulatory regions. STV analysis found a significant association with replication timing and identified known (CDKN2A, CCND1, APC, and TERT) and new (ASH1L, NCOR1, and MACROD2) cancer-related genes that were recurrently affected by STVs, leading to altered expression. These results emphasize the value of whole-genome sequencing analysis in discovering cancer driver mutations and understanding comprehensive molecular profiles of liver cancer, especially with regard to STVs and noncoding mutations.

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Comment in

Whole-genome mutational analysis: cause and effect of noncoding and structural mutations in liver cancer.
Ghosh S, Banerjee S. Ghosh S, et al. Hepatobiliary Surg Nutr. 2017 Feb;6(1):57-59. doi: 10.21037/hbsn.2017.01.03. Hepatobiliary Surg Nutr. 2017. PMID: 28261598 Free PMC article. No abstract available.
Regulome networks and mutational landscape in liver cancer: An informative path to precision medicine.
Yi S, Sahni N. Yi S, et al. Hepatology. 2017 Jul;66(1):280-282. doi: 10.1002/hep.29220. Epub 2017 Jun 7. Hepatology. 2017. PMID: 28422313 Free PMC article. No abstract available.

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Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer

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Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer

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Affiliations

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