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Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

Author

Listed:
  • Swee Seong Wong

    (Lilly Research Labs, Eli Lilly and Co)

  • Kyoung-Mee Kim

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • Jason C. Ting

    (Lilly Research Labs, Eli Lilly and Co)

  • Kun Yu

    (Lilly Research Labs, Eli Lilly and Co
    Present address: Novartis Institute for Biomedical Research, Boston, Massachusetts, USA)

  • Jake Fu

    (Shanghai Biocorp)

  • Shawn Liu

    (BGI Techsolutions)

  • Razvan Cristescu

    (Merck Research Labs, Merck Sharpe & Dohme)

  • Michael Nebozhyn

    (Merck Research Labs, Merck Sharpe & Dohme)

  • Lara Gong

    (BGI Techsolutions)

  • Yong Gang Yue

    (Lilly Research Labs, Eli Lilly and Co)

  • Jian Wang

    (Lilly Research Labs, Eli Lilly and Co)

  • Chen Ronghua

    (Merck Research Labs, Merck Sharpe & Dohme)

  • Andrey Loboda

    (Merck Research Labs, Merck Sharpe & Dohme)

  • James Hardwick

    (Merck Research Labs, Merck Sharpe & Dohme
    Present address: Pfizer, San Diego, California, USA)

  • Xiaoqiao Liu

    (Merck Research Labs, Merck Sharpe & Dohme)

  • Hongyue Dai

    (Merck Research Labs, Merck Sharpe & Dohme)

  • Jason Gang Jin

    (Shanghai Biocorp)

  • Xiang S. Ye

    (Lilly Research Labs, Eli Lilly and Co)

  • So Young Kang

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • In Gu Do

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • Joon Oh Park

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • Tae Sung Sohn

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • Christoph Reinhard

    (Lilly Research Labs, Eli Lilly and Co)

  • Jeeyun Lee

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • Sung Kim

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • Amit Aggarwal

    (Lilly Research Labs, Eli Lilly and Co)

Abstract

Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.

Suggested Citation

  • Swee Seong Wong & Kyoung-Mee Kim & Jason C. Ting & Kun Yu & Jake Fu & Shawn Liu & Razvan Cristescu & Michael Nebozhyn & Lara Gong & Yong Gang Yue & Jian Wang & Chen Ronghua & Andrey Loboda & James Har, 2014. "Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6477
    DOI: 10.1038/ncomms6477
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    Cited by:

    1. Xue-Ke Zhao & Pengwei Xing & Xin Song & Miao Zhao & Linxuan Zhao & Yonglong Dang & Ling-Ling Lei & Rui-Hua Xu & Wen-Li Han & Pan-Pan Wang & Miao-Miao Yang & Jing-Feng Hu & Kan Zhong & Fu-You Zhou & Xu, 2021. "Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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