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Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas

Author

Listed:
  • Luis Jaime Castro-Vega

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine)

  • Eric Letouzé

    (Programme Cartes d’Identité des Tumeurs, Ligue Nationale Contre Le Cancer)

  • Nelly Burnichon

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou)

  • Alexandre Buffet

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou)

  • Pierre-Hélie Disderot

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine)

  • Emmanuel Khalifa

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou)

  • Céline Loriot

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine)

  • Nabila Elarouci

    (Programme Cartes d’Identité des Tumeurs, Ligue Nationale Contre Le Cancer)

  • Aurélie Morin

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine)

  • Mélanie Menara

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine)

  • Charlotte Lepoutre-Lussey

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Hypertension Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou)

  • Cécile Badoual

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou)

  • Mathilde Sibony

    (Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Cochin)

  • Bertrand Dousset

    (Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Cochin
    INSERM, U1016, Institut Cochin
    CNRS UMR8104)

  • Rossella Libé

    (Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    INSERM, U1016, Institut Cochin
    CNRS UMR8104
    Assistance Publique-Hôpitaux de Paris, Hôpital Cochin)

  • Franck Zinzindohoue

    (Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou)

  • Pierre François Plouin

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Hypertension Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou
    Rare Adrenal Cancer Network COMETE)

  • Jérôme Bertherat

    (Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    INSERM, U1016, Institut Cochin
    CNRS UMR8104
    Assistance Publique-Hôpitaux de Paris, Hôpital Cochin)

  • Laurence Amar

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Hypertension Unit, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou)

  • Aurélien de Reyniès

    (Programme Cartes d’Identité des Tumeurs, Ligue Nationale Contre Le Cancer)

  • Judith Favier

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine)

  • Anne-Paule Gimenez-Roqueplo

    (INSERM, UMR970, Paris-Cardiovascular Research Center
    Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou
    Rare Adrenal Cancer Network COMETE)

Abstract

Pheochromocytomas and paragangliomas (PCCs/PGLs) are neural crest-derived tumours with a very strong genetic component. Here we report the first integrated genomic examination of a large collection of PCC/PGL. SNP array analysis reveals distinct copy-number patterns associated with genetic background. Whole-exome sequencing shows a low mutation rate of 0.3 mutations per megabase, with few recurrent somatic mutations in genes not previously associated with PCC/PGL. DNA methylation arrays and miRNA sequencing identify DNA methylation changes and miRNA expression clusters strongly associated with messenger RNA expression profiling. Overexpression of the miRNA cluster 182/96/183 is specific in SDHB-mutated tumours and induces malignant traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster appears as a potential driver in a subgroup of sporadic tumours. Altogether, the complete genomic landscape of PCC/PGL is mainly driven by distinct germline and/or somatic mutations in susceptibility genes and reveals different molecular entities, characterized by a set of unique genomic alterations.

Suggested Citation

  • Luis Jaime Castro-Vega & Eric Letouzé & Nelly Burnichon & Alexandre Buffet & Pierre-Hélie Disderot & Emmanuel Khalifa & Céline Loriot & Nabila Elarouci & Aurélie Morin & Mélanie Menara & Charlotte Lep, 2015. "Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7044
    DOI: 10.1038/ncomms7044
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