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Exploring the landscape of focal amplifications in cancer using AmpliconArchitect

Author

Listed:
  • Viraj Deshpande

    (University of California at San Diego)

  • Jens Luebeck

    (University of California at San Diego)

  • Nam-Phuong D. Nguyen

    (University of California at San Diego)

  • Mehrdad Bakhtiari

    (University of California at San Diego)

  • Kristen M. Turner

    (University of California at San Diego)

  • Richard Schwab

    (University of California at San Diego)

  • Hannah Carter

    (University of California at San Diego
    University of California at San Diego)

  • Paul S. Mischel

    (University of California at San Diego
    University of California at San Diego
    University of California, San Diego)

  • Vineet Bafna

    (University of California at San Diego)

Abstract

Focal oncogene amplification and rearrangements drive tumor growth and evolution in multiple cancer types. We present AmpliconArchitect (AA), a tool to reconstruct the fine structure of focally amplified regions using whole genome sequencing (WGS) and validate it extensively on multiple simulated and real datasets, across a wide range of coverage and copy numbers. Analysis of AA-reconstructed amplicons in a pan-cancer dataset reveals many novel properties of copy number amplifications in cancer. These findings support a model in which focal amplifications arise due to the formation and replication of extrachromosomal DNA. Applying AA to 68 viral-mediated cancer samples, we identify a large fraction of amplicons with specific structural signatures suggestive of hybrid, human-viral extrachromosomal DNA. AA reconstruction, integrated with metaphase fluorescence in situ hybridization (FISH) and PacBio sequencing on the cell-line UPCI:SCC090 confirm the extrachromosomal origin and fine structure of a Forkhead box E1 (FOXE1)-containing hybrid amplicon.

Suggested Citation

  • Viraj Deshpande & Jens Luebeck & Nam-Phuong D. Nguyen & Mehrdad Bakhtiari & Kristen M. Turner & Richard Schwab & Hannah Carter & Paul S. Mischel & Vineet Bafna, 2019. "Exploring the landscape of focal amplifications in cancer using AmpliconArchitect," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08200-y
    DOI: 10.1038/s41467-018-08200-y
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    Cited by:

    1. Qionghua Zhu & Xin Zhao & Yuanhang Zhang & Yanping Li & Shang Liu & Jingxuan Han & Zhiyuan Sun & Chunqing Wang & Daqi Deng & Shanshan Wang & Yisen Tang & Yaling Huang & Siyuan Jiang & Chi Tian & Xi Ch, 2023. "Single cell multi-omics reveal intra-cell-line heterogeneity across human cancer cell lines," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Shixiang Wang & Chen-Yi Wu & Ming-Ming He & Jia-Xin Yong & Yan-Xing Chen & Li-Mei Qian & Jin-Ling Zhang & Zhao-Lei Zeng & Rui-Hua Xu & Feng Wang & Qi Zhao, 2024. "Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Mihoko Saito-Adachi & Natsuko Hama & Yasushi Totoki & Hiromi Nakamura & Yasuhito Arai & Fumie Hosoda & Hirofumi Rokutan & Shinichi Yachida & Mamoru Kato & Akihiko Fukagawa & Tatsuhiro Shibata, 2023. "Oncogenic structural aberration landscape in gastric cancer genomes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Alvin Wei Tian Ng & Dylan Peter McClurg & Ben Wesley & Shahriar A. Zamani & Emily Black & Ahmad Miremadi & Olivier Giger & Rogier ten Hoopen & Ginny Devonshire & Aisling M. Redmond & Nicola Grehan & S, 2024. "Disentangling oncogenic amplicons in esophageal adenocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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