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The genomic landscape of tuberous sclerosis complex

Author

Listed:
  • Katie R. Martin

    (Center for Cancer and Cell Biology, Van Andel Research Institute)

  • Wanding Zhou

    (Center for Epigenetics, Van Andel Research Institute)

  • Megan J. Bowman

    (Bioinformatics and Biostatistics Core, Van Andel Research Institute)

  • Juliann Shih

    (Cancer Program, Broad Institute of Harvard and MIT)

  • Kit Sing Au

    (University of Texas Health Science Center at Houston-McGovern Medical School)

  • Kristin E. Dittenhafer-Reed

    (Center for Cancer and Cell Biology, Van Andel Research Institute)

  • Kellie A. Sisson

    (Center for Cancer and Cell Biology, Van Andel Research Institute)

  • Julie Koeman

    (Cytogenetics and Pathology Core, Van Andel Research Institute)

  • Daniel J. Weisenberger

    (Norris Comprehensive Cancer Center, University of Southern California)

  • Sandra L. Cottingham

    (Spectrum Health System)

  • Steven T. DeRoos

    (Helen DeVos Children’s Hospital, Spectrum Health System)

  • Orrin Devinsky

    (New York University School of Medicine)

  • Mary E. Winn

    (Bioinformatics and Biostatistics Core, Van Andel Research Institute)

  • Andrew D. Cherniack

    (Cancer Program, Broad Institute of Harvard and MIT)

  • Hui Shen

    (Center for Epigenetics, Van Andel Research Institute)

  • Hope Northrup

    (University of Texas Health Science Center at Houston-McGovern Medical School)

  • Darcy A. Krueger

    (Cincinnati Children’s Hospital Medical Center)

  • Jeffrey P. MacKeigan

    (Center for Cancer and Cell Biology, Van Andel Research Institute
    College of Human Medicine, Michigan State University)

Abstract

Tuberous sclerosis complex (TSC) is a rare genetic disease causing multisystem growth of benign tumours and other hamartomatous lesions, which leads to diverse and debilitating clinical symptoms. Patients are born with TSC1 or TSC2 mutations, and somatic inactivation of wild-type alleles drives MTOR activation; however, second hits to TSC1/TSC2 are not always observed. Here, we present the genomic landscape of TSC hamartomas. We determine that TSC lesions contain a low somatic mutational burden relative to carcinomas, a subset feature large-scale chromosomal aberrations, and highly conserved molecular signatures for each type exist. Analysis of the molecular signatures coupled with computational approaches reveals unique aspects of cellular heterogeneity and cell origin. Using immune data sets, we identify significant neuroinflammation in TSC-associated brain tumours. Taken together, this molecular catalogue of TSC serves as a resource into the origin of these hamartomas and provides a framework that unifies genomic and transcriptomic dimensions for complex tumours.

Suggested Citation

  • Katie R. Martin & Wanding Zhou & Megan J. Bowman & Juliann Shih & Kit Sing Au & Kristin E. Dittenhafer-Reed & Kellie A. Sisson & Julie Koeman & Daniel J. Weisenberger & Sandra L. Cottingham & Steven T, 2017. "The genomic landscape of tuberous sclerosis complex," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15816
    DOI: 10.1038/ncomms15816
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    Cited by:

    1. Yan Tang & David J. Kwiatkowski & Elizabeth P. Henske, 2022. "Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. J. O. R. Hernandez & X. Wang & M. Vazquez-Segoviano & M. Lopez-Marfil & M. F. Sobral-Reyes & A. Moran-Horowich & M. Sundberg & D. O. Lopez-Cantu & C. K. Probst & G. U. Ruiz-Esparza & K. Giannikou & R., 2021. "A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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