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RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer

Author

Listed:
  • Matthew J. Niederst

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Lecia V. Sequist

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • John T. Poirier

    (Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service)

  • Craig H. Mermel

    (Broad Institute of MIT and Harvard, Cancer Genome Comparative Analysis Group
    Massachusetts General Hospital Cancer Center)

  • Elizabeth L. Lockerman

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Angel R. Garcia

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Ryohei Katayama

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Carlotta Costa

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Kenneth N. Ross

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Teresa Moran

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School
    Present address: Catalan Institute of Oncology, Avinguda de la Granvia de l’Hospitalet, 199-203, 08907 Barcelona, Spain)

  • Emily Howe

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Linnea E. Fulton

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Hillary E. Mulvey

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Lindsay A. Bernardo

    (Massachusetts General Hospital Cancer Center
    Harvard Medical School)

  • Farhiya Mohamoud

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Norikatsu Miyoshi

    (Harvard Medical School
    Molecular Profiling Laboratory, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital)

  • Paul A. VanderLaan

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Daniel B. Costa

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Pasi A. Jänne

    (Belfer Institute of Applied Science, Dana Farber Cancer Institute
    Brigham and Women’s Hospital and Harvard Medical School)

  • Darrell R. Borger

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

  • Sridhar Ramaswamy

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard, Cancer Genome Comparative Analysis Group)

  • Toshi Shioda

    (Harvard Medical School
    Molecular Profiling Laboratory, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital)

  • Anthony J. Iafrate

    (Massachusetts General Hospital Cancer Center
    Harvard Medical School)

  • Gad Getz

    (Harvard Medical School
    Broad Institute of MIT and Harvard, Cancer Genome Comparative Analysis Group
    Massachusetts General Hospital Cancer Center)

  • Charles M. Rudin

    (Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service)

  • Mari Mino-Kenudson

    (Massachusetts General Hospital Cancer Center
    Harvard Medical School)

  • Jeffrey A. Engelman

    (Massachusetts General Hospital Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

Abstract

Tyrosine kinase inhibitors are effective treatments for non-small-cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, relapse typically occurs after an average of 1 year of continuous treatment. A fundamental histological transformation from NSCLC to small-cell lung cancer (SCLC) is observed in a subset of the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of tumour samples and cell lines derived from resistant EGFR mutant patients revealed that Retinoblastoma (RB) is lost in 100% of these SCLC transformed cases, but rarely in those that remain NSCLC. Further, increased neuroendocrine marker and decreased EGFR expression as well as greater sensitivity to BCL2 family inhibition are observed in resistant SCLC transformed cancers compared with resistant NSCLCs. Together, these findings suggest that this subset of resistant cancers ultimately adopt many of the molecular and phenotypic characteristics of classical SCLC.

Suggested Citation

  • Matthew J. Niederst & Lecia V. Sequist & John T. Poirier & Craig H. Mermel & Elizabeth L. Lockerman & Angel R. Garcia & Ryohei Katayama & Carlotta Costa & Kenneth N. Ross & Teresa Moran & Emily Howe &, 2015. "RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7377
    DOI: 10.1038/ncomms7377
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    Cited by:

    1. Ming Tang & Hussein A. Abbas & Marcelo V. Negrao & Maheshwari Ramineni & Xin Hu & Shawna Marie Hubert & Junya Fujimoto & Alexandre Reuben & Susan Varghese & Jianhua Zhang & Jun Li & Chi-Wan Chow & Xiz, 2021. "The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Han Wang & Huiying Sun & Bilin Liang & Fang Zhang & Fan Yang & Bowen Cui & Lixia Ding & Xiang Wang & Ronghua Wang & Jiaoyang Cai & Yanjing Tang & Jianan Rao & Wenting Hu & Shuang Zhao & Wenyan Wu & Xi, 2023. "Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Anna-Lisa Doebley & Minjeong Ko & Hanna Liao & A. Eden Cruikshank & Katheryn Santos & Caroline Kikawa & Joseph B. Hiatt & Robert D. Patton & Navonil De Sarkar & Katharine A. Collier & Anna C. H. Hoge , 2022. "A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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