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The fusion landscape of hepatocellular carcinoma

Most cases of hepatocellular carcinoma (HCC) are already advanced at the time of diagnosis, which limits treatment options. Challenges in early‐stage diagnosis may be due to the genetic complexity of HCC. Gene fusion plays a critical function in tumorigenesis and cancer progression in multiple cance...

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Autores principales: Zhu, Chengpei, Wu, Liangcai, Lv, Yanling, Guan, Jinxia, Bai, Xue, Lin, Jianzhen, Liu, Tingting, Yang, Xiaobo, Robson, Simon C., Sang, Xinting, Xue, Chenghai, Zhao, Haitao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487730/
https://www.ncbi.nlm.nih.gov/pubmed/30903738
http://dx.doi.org/10.1002/1878-0261.12479
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author Zhu, Chengpei
Wu, Liangcai
Lv, Yanling
Guan, Jinxia
Bai, Xue
Lin, Jianzhen
Liu, Tingting
Yang, Xiaobo
Robson, Simon C.
Sang, Xinting
Xue, Chenghai
Zhao, Haitao
author_facet Zhu, Chengpei
Wu, Liangcai
Lv, Yanling
Guan, Jinxia
Bai, Xue
Lin, Jianzhen
Liu, Tingting
Yang, Xiaobo
Robson, Simon C.
Sang, Xinting
Xue, Chenghai
Zhao, Haitao
author_sort Zhu, Chengpei
collection PubMed
description Most cases of hepatocellular carcinoma (HCC) are already advanced at the time of diagnosis, which limits treatment options. Challenges in early‐stage diagnosis may be due to the genetic complexity of HCC. Gene fusion plays a critical function in tumorigenesis and cancer progression in multiple cancers, yet the identities of fusion genes as potential diagnostic markers in HCC have not been investigated. Here, we employed STAR‐Fusion and identified 43 recurrent fusion events in our own and four public RNA‐seq datasets. We identified 2354 different gene fusions in two hepatitis B virus (HBV)‐HCC patients. Validation analysis against the four RNA‐seq datasets revealed that only 1.8% (43/2354) were recurrent fusions. Comparison with the four fusion databases demonstrated that 19 recurrent fusions were not previously annotated to diseases and three were annotated as disease‐related fusion events. Finally, we validated six of the novel fusion events, including RP11‐476K15.1‐CTD‐2015H3.2, by RT‐PCR and Sanger sequencing of 14 pairs of HBV‐related HCC samples. In summary, our study provides new insights into gene fusions in HCC and may contribute to the development of anti‐HCC therapy.
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spelling pubmed-64877302019-05-07 The fusion landscape of hepatocellular carcinoma Zhu, Chengpei Wu, Liangcai Lv, Yanling Guan, Jinxia Bai, Xue Lin, Jianzhen Liu, Tingting Yang, Xiaobo Robson, Simon C. Sang, Xinting Xue, Chenghai Zhao, Haitao Mol Oncol Research Articles Most cases of hepatocellular carcinoma (HCC) are already advanced at the time of diagnosis, which limits treatment options. Challenges in early‐stage diagnosis may be due to the genetic complexity of HCC. Gene fusion plays a critical function in tumorigenesis and cancer progression in multiple cancers, yet the identities of fusion genes as potential diagnostic markers in HCC have not been investigated. Here, we employed STAR‐Fusion and identified 43 recurrent fusion events in our own and four public RNA‐seq datasets. We identified 2354 different gene fusions in two hepatitis B virus (HBV)‐HCC patients. Validation analysis against the four RNA‐seq datasets revealed that only 1.8% (43/2354) were recurrent fusions. Comparison with the four fusion databases demonstrated that 19 recurrent fusions were not previously annotated to diseases and three were annotated as disease‐related fusion events. Finally, we validated six of the novel fusion events, including RP11‐476K15.1‐CTD‐2015H3.2, by RT‐PCR and Sanger sequencing of 14 pairs of HBV‐related HCC samples. In summary, our study provides new insights into gene fusions in HCC and may contribute to the development of anti‐HCC therapy. John Wiley and Sons Inc. 2019-04-11 2019-05 /pmc/articles/PMC6487730/ /pubmed/30903738 http://dx.doi.org/10.1002/1878-0261.12479 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zhu, Chengpei
Wu, Liangcai
Lv, Yanling
Guan, Jinxia
Bai, Xue
Lin, Jianzhen
Liu, Tingting
Yang, Xiaobo
Robson, Simon C.
Sang, Xinting
Xue, Chenghai
Zhao, Haitao
The fusion landscape of hepatocellular carcinoma
title The fusion landscape of hepatocellular carcinoma
title_full The fusion landscape of hepatocellular carcinoma
title_fullStr The fusion landscape of hepatocellular carcinoma
title_full_unstemmed The fusion landscape of hepatocellular carcinoma
title_short The fusion landscape of hepatocellular carcinoma
title_sort fusion landscape of hepatocellular carcinoma
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487730/
https://www.ncbi.nlm.nih.gov/pubmed/30903738
http://dx.doi.org/10.1002/1878-0261.12479
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