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

Akihiro Fujimoto; Mayuko Furuta; Yasushi Totoki; Tatsuhiko Tsunoda; Mamoru Kato; Yuichi Shiraishi; Hiroko Tanaka; Hiroaki Taniguchi; Yoshiiku Kawakami; Masaki Ueno; Kunihito Gotoh; Shun Ichi Ariizumi; Christopher P. Wardell; Shinya Hayami; Toru Nakamura; Hiroshi Aikata; Koji Arihiro; Keith A. Boroevich; Tetsuo Abe; Kaoru Nakano; Kazuhiro Maejima; Aya Sasaki-Oku; Ayako Ohsawa; Tetsuo Shibuya; Hiromi Nakamura; Natsuko Hama; Fumie Hosoda; Yasuhito Arai; Shoko Ohashi; Tomoko Urushidate; Genta Nagae; Shogo Yamamoto; Hiroki Ueda; Kenji Tatsuno; Hidenori Ojima; Nobuyoshi Hiraoka; Takuji Okusaka; Michiaki Kubo; Shigeru Marubashi; Terumasa Yamada; Satoshi Hirano; Masakazu Yamamoto; Hideki Ohdan; Kazuaki Shimada; Osamu Ishikawa; Hiroki Yamaue; Kazuki Chayama; Satoru Miyano; Hiroyuki Aburatani; Tatsuhiro Shibata; Hidewaki Nakagawa

doi:10.1038/ng.3547

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

Akihiro Fujimoto, Mayuko Furuta, Yasushi Totoki, Tatsuhiko Tsunoda, Mamoru Kato, Yuichi Shiraishi, Hiroko Tanaka, Hiroaki Taniguchi, Yoshiiku Kawakami, Masaki Ueno, Kunihito Gotoh, Shun Ichi Ariizumi, Christopher P. Wardell, Shinya Hayami, Toru Nakamura, Hiroshi Aikata, Koji Arihiro, Keith A. Boroevich, Tetsuo Abe, Kaoru NakanoKazuhiro Maejima, Aya Sasaki-Oku, Ayako Ohsawa, Tetsuo Shibuya, Hiromi Nakamura, Natsuko Hama, Fumie Hosoda, Yasuhito Arai, Shoko Ohashi, Tomoko Urushidate, Genta Nagae, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Hidenori Ojima, Nobuyoshi Hiraoka, Takuji Okusaka, Michiaki Kubo, Shigeru Marubashi, Terumasa Yamada, Satoshi Hirano, Masakazu Yamamoto, Hideki Ohdan, Kazuaki Shimada, Osamu Ishikawa, Hiroki Yamaue, Kazuki Chayama, Satoru Miyano, Hiroyuki Aburatani, Tatsuhiro Shibata, Hidewaki Nakagawa

Research output: Contribution to journal › Article › peer-review

545 Citations (Scopus)

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.

Original language	English
Pages (from-to)	500-509
Number of pages	10
Journal	Nature Genetics
Volume	48
Issue number	5
DOIs	https://doi.org/10.1038/ng.3547
Publication status	Published - 01-05-2016
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Fujimoto, A., Furuta, M., Totoki, Y., Tsunoda, T., Kato, M., Shiraishi, Y., Tanaka, H., Taniguchi, H., Kawakami, Y., Ueno, M., Gotoh, K., Ariizumi, S. I., Wardell, C. P., Hayami, S., Nakamura, T., Aikata, H., Arihiro, K., Boroevich, K. A., Abe, T., ... Nakagawa, H. (2016). Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. Nature Genetics, 48(5), 500-509. https://doi.org/10.1038/ng.3547

@article{e1c4557ac07f477a802c8a0123f695eb,

title = "Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer",

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.",

author = "Akihiro Fujimoto and Mayuko Furuta and Yasushi Totoki and Tatsuhiko Tsunoda and Mamoru Kato and Yuichi Shiraishi and Hiroko Tanaka and Hiroaki Taniguchi and Yoshiiku Kawakami and Masaki Ueno and Kunihito Gotoh and Ariizumi, {Shun Ichi} and Wardell, {Christopher P.} and Shinya Hayami and Toru Nakamura and Hiroshi Aikata and Koji Arihiro and Boroevich, {Keith A.} and Tetsuo Abe and Kaoru Nakano and Kazuhiro Maejima and Aya Sasaki-Oku and Ayako Ohsawa and Tetsuo Shibuya and Hiromi Nakamura and Natsuko Hama and Fumie Hosoda and Yasuhito Arai and Shoko Ohashi and Tomoko Urushidate and Genta Nagae and Shogo Yamamoto and Hiroki Ueda and Kenji Tatsuno and Hidenori Ojima and Nobuyoshi Hiraoka and Takuji Okusaka and Michiaki Kubo and Shigeru Marubashi and Terumasa Yamada and Satoshi Hirano and Masakazu Yamamoto and Hideki Ohdan and Kazuaki Shimada and Osamu Ishikawa and Hiroki Yamaue and Kazuki Chayama and Satoru Miyano and Hiroyuki Aburatani and Tatsuhiro Shibata and Hidewaki Nakagawa",

note = "Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",

year = "2016",

month = may,

day = "1",

doi = "10.1038/ng.3547",

language = "English",

volume = "48",

pages = "500--509",

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Fujimoto, A, Furuta, M, Totoki, Y, Tsunoda, T, Kato, M, Shiraishi, Y, Tanaka, H, Taniguchi, H, Kawakami, Y, Ueno, M, Gotoh, K, Ariizumi, SI, 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 2016, 'Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer', Nature Genetics, vol. 48, no. 5, pp. 500-509. https://doi.org/10.1038/ng.3547

TY - JOUR

T1 - Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer

AU - Fujimoto, Akihiro

AU - Furuta, Mayuko

AU - Totoki, Yasushi

AU - Tsunoda, Tatsuhiko

AU - Kato, Mamoru

AU - Shiraishi, Yuichi

AU - Tanaka, Hiroko

AU - Taniguchi, Hiroaki

AU - Kawakami, Yoshiiku

AU - Ueno, Masaki

AU - Gotoh, Kunihito

AU - Ariizumi, Shun Ichi

AU - Wardell, Christopher P.

AU - Hayami, Shinya

AU - Nakamura, Toru

AU - Aikata, Hiroshi

AU - Arihiro, Koji

AU - Boroevich, Keith A.

AU - Abe, Tetsuo

AU - Nakano, Kaoru

AU - Maejima, Kazuhiro

AU - Sasaki-Oku, Aya

AU - Ohsawa, Ayako

AU - Shibuya, Tetsuo

AU - Nakamura, Hiromi

AU - Hama, Natsuko

AU - Hosoda, Fumie

AU - Arai, Yasuhito

AU - Ohashi, Shoko

AU - Urushidate, Tomoko

AU - Nagae, Genta

AU - Yamamoto, Shogo

AU - Ueda, Hiroki

AU - Tatsuno, Kenji

AU - Ojima, Hidenori

AU - Hiraoka, Nobuyoshi

AU - Okusaka, Takuji

AU - Kubo, Michiaki

AU - Marubashi, Shigeru

AU - Yamada, Terumasa

AU - Hirano, Satoshi

AU - Yamamoto, Masakazu

AU - Ohdan, Hideki

AU - Shimada, Kazuaki

AU - Ishikawa, Osamu

AU - Yamaue, Hiroki

AU - Chayama, Kazuki

AU - Miyano, Satoru

AU - Aburatani, Hiroyuki

AU - Shibata, Tatsuhiro

AU - Nakagawa, Hidewaki

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84963588792&partnerID=8YFLogxK

U2 - 10.1038/ng.3547

DO - 10.1038/ng.3547

M3 - Article

C2 - 27064257

AN - SCOPUS:84963588792

SN - 1061-4036

VL - 48

SP - 500

EP - 509

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

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