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Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations

Author

Listed:
  • Yvonne Y Li

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT)

  • Grace T. Y. Chung

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Vivian W. Y. Lui

    (School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong
    School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Ka-Fai To

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Brigette B. Y. Ma

    (State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong)

  • Chit Chow

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • John K, S. Woo

    (Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong)

  • Kevin Y. Yip

    (The Chinese University of Hong Kong)

  • Jeongsun Seo

    (Genomic Medicine Institute, Medical Research Center, Seoul National University)

  • Edwin P. Hui

    (State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong)

  • Michael K. F. Mak

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Maria Rusan

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT)

  • Nicole G. Chau

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT)

  • Yvonne Y. Y. Or

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Marcus H. N. Law

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Peggy P. Y. Law

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Zoey W. Y. Liu

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Hoi-Lam Ngan

    (School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Pok-Man Hau

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Krista R. Verhoeft

    (School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Peony H. Y. Poon

    (School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Seong-Keun Yoo

    (Genomic Medicine Institute, Medical Research Center, Seoul National University)

  • Jong-Yeon Shin

    (Genomic Medicine Institute, Medical Research Center, Seoul National University)

  • Sau-Dan Lee

    (The Chinese University of Hong Kong)

  • Samantha W. M. Lun

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Lin Jia

    (School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Anthony W. H. Chan

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

  • Jason Y. K. Chan

    (Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong)

  • Paul B. S. Lai

    (Prince of Wales Hospital, The Chinese University of Hong Kong)

  • Choi-Yi Fung

    (School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Suet-Ting Hung

    (School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Lin Wang

    (University of Pittsburgh Medical Center)

  • Ann Margaret V. Chang

    (Institute of Pathology, St. Luke’s Medical Center)

  • Simion I. Chiosea

    (University of Pittsburgh Medical Center)

  • Matthew L. Hedberg

    (Medical Scientist Training Program, University of Pittsburgh–Carnegie Mellon University)

  • Sai-Wah Tsao

    (School of Biomedical Sciences and Center for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Andrew C. van Hasselt

    (Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong)

  • Anthony T. C. Chan

    (State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong)

  • Jennifer R. Grandis

    (University of California San Francisco)

  • Peter S. Hammerman

    (Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, Cancer Program, Broad Institute of Harvard and MIT)

  • Kwok-Wai Lo

    (State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong)

Abstract

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.

Suggested Citation

  • Yvonne Y Li & Grace T. Y. Chung & Vivian W. Y. Lui & Ka-Fai To & Brigette B. Y. Ma & Chit Chow & John K, S. Woo & Kevin Y. Yip & Jeongsun Seo & Edwin P. Hui & Michael K. F. Mak & Maria Rusan & Nicole , 2017. "Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14121
    DOI: 10.1038/ncomms14121
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    Cited by:

    1. Darren Wan-Teck Lim & Hsiang-Fong Kao & Lisda Suteja & Constance H. Li & Hong Sheng Quah & Daniel Shao-Weng Tan & Sze-Huey Tan & Eng-Huat Tan & Wan-Ling Tan & Justina Nadia Lee & Felicia Yu-Ting Wee &, 2023. "Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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