Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.
Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4272259?pdf=render |
| _version_ | 1811281450545184768 |
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| author | Yuichi Shiraishi Akihiro Fujimoto Mayuko Furuta Hiroko Tanaka Ken-ichi Chiba Keith A Boroevich Tetsuo Abe Yoshiiku Kawakami Masaki Ueno Kunihito Gotoh Shun-ichi Ariizumi Tetsuo Shibuya Kaoru Nakano Aya Sasaki Kazuhiro Maejima Rina Kitada Shinya Hayami Yoshinobu Shigekawa Shigeru Marubashi Terumasa Yamada Michiaki Kubo Osamu Ishikawa Hiroshi Aikata Koji Arihiro Hideki Ohdan Masakazu Yamamoto Hiroki Yamaue Kazuaki Chayama Tatsuhiko Tsunoda Satoru Miyano Hidewaki Nakagawa |
| author_facet | Yuichi Shiraishi Akihiro Fujimoto Mayuko Furuta Hiroko Tanaka Ken-ichi Chiba Keith A Boroevich Tetsuo Abe Yoshiiku Kawakami Masaki Ueno Kunihito Gotoh Shun-ichi Ariizumi Tetsuo Shibuya Kaoru Nakano Aya Sasaki Kazuhiro Maejima Rina Kitada Shinya Hayami Yoshinobu Shigekawa Shigeru Marubashi Terumasa Yamada Michiaki Kubo Osamu Ishikawa Hiroshi Aikata Koji Arihiro Hideki Ohdan Masakazu Yamamoto Hiroki Yamaue Kazuaki Chayama Tatsuhiko Tsunoda Satoru Miyano Hidewaki Nakagawa |
| author_sort | Yuichi Shiraishi |
| collection | DOAJ |
| description | Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) and their matched controls. Comparison of whole genome sequence (WGS) and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3), and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome. |
| first_indexed | 2024-04-13T01:32:47Z |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T01:32:47Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-0c55b6ffd2204e638d6be890c00cc1ac2022-12-22T03:08:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11426310.1371/journal.pone.0114263Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.Yuichi ShiraishiAkihiro FujimotoMayuko FurutaHiroko TanakaKen-ichi ChibaKeith A BoroevichTetsuo AbeYoshiiku KawakamiMasaki UenoKunihito GotohShun-ichi AriizumiTetsuo ShibuyaKaoru NakanoAya SasakiKazuhiro MaejimaRina KitadaShinya HayamiYoshinobu ShigekawaShigeru MarubashiTerumasa YamadaMichiaki KuboOsamu IshikawaHiroshi AikataKoji ArihiroHideki OhdanMasakazu YamamotoHiroki YamaueKazuaki ChayamaTatsuhiko TsunodaSatoru MiyanoHidewaki NakagawaRecent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) and their matched controls. Comparison of whole genome sequence (WGS) and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3), and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.http://europepmc.org/articles/PMC4272259?pdf=render |
| spellingShingle | Yuichi Shiraishi Akihiro Fujimoto Mayuko Furuta Hiroko Tanaka Ken-ichi Chiba Keith A Boroevich Tetsuo Abe Yoshiiku Kawakami Masaki Ueno Kunihito Gotoh Shun-ichi Ariizumi Tetsuo Shibuya Kaoru Nakano Aya Sasaki Kazuhiro Maejima Rina Kitada Shinya Hayami Yoshinobu Shigekawa Shigeru Marubashi Terumasa Yamada Michiaki Kubo Osamu Ishikawa Hiroshi Aikata Koji Arihiro Hideki Ohdan Masakazu Yamamoto Hiroki Yamaue Kazuaki Chayama Tatsuhiko Tsunoda Satoru Miyano Hidewaki Nakagawa Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. PLoS ONE |
| title | Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. |
| title_full | Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. |
| title_fullStr | Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. |
| title_full_unstemmed | Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. |
| title_short | Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. |
| title_sort | integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers |
| url | http://europepmc.org/articles/PMC4272259?pdf=render |
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