A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition

Santiago Ropero, Mario F Fraga, Esteban Ballestar, Richard Hamelin, Hiroyuki Yamamoto, Manuel Boix-Chornet, Rosalia Caballero, Miguel Alaminos, Fernando Setien, Maria F Paz, Michel Herranz, Jose Palacios, Diego Arango, Torben F Ørntoft, Lauri A Aaltonen, Simo Schwartz, Manel Esteller

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Disruption of histone acetylation patterns is a common feature of cancer cells, but very little is known about its genetic basis. We have identified truncating mutations in one of the primary human histone deacetylases, HDAC2, in sporadic carcinomas with microsatellite instability and in tumors arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. The presence of the HDAC2 frameshift mutation causes a loss of HDAC2 protein expression and enzymatic activity and renders these cells more resistant to the usual antiproliferative and proapoptotic effects of histone deacetylase inhibitors. As such drugs may serve as therapeutic agents for cancer, our findings support the use of HDAC2 mutational status in future pharmacogenetic treatment of these individuals.
    Original languageEnglish
    JournalNature Genetics
    Volume38
    Issue number5
    Pages (from-to)566-569
    Number of pages4
    ISSN1061-4036
    DOIs
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Ropero, S., Fraga, M. F., Ballestar, E., Hamelin, R., Yamamoto, H., Boix-Chornet, M., ... Esteller, M. (2006). A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Nature Genetics, 38(5), 566-569. https://doi.org/10.1038/ng1773
    Ropero, Santiago ; Fraga, Mario F ; Ballestar, Esteban ; Hamelin, Richard ; Yamamoto, Hiroyuki ; Boix-Chornet, Manuel ; Caballero, Rosalia ; Alaminos, Miguel ; Setien, Fernando ; Paz, Maria F ; Herranz, Michel ; Palacios, Jose ; Arango, Diego ; Ørntoft, Torben F ; Aaltonen, Lauri A ; Schwartz, Simo ; Esteller, Manel. / A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. In: Nature Genetics. 2006 ; Vol. 38, No. 5. pp. 566-569.
    @article{fd6e75338e1e4464ab72a73e8d0b2b80,
    title = "A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition",
    abstract = "Disruption of histone acetylation patterns is a common feature of cancer cells, but very little is known about its genetic basis. We have identified truncating mutations in one of the primary human histone deacetylases, HDAC2, in sporadic carcinomas with microsatellite instability and in tumors arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. The presence of the HDAC2 frameshift mutation causes a loss of HDAC2 protein expression and enzymatic activity and renders these cells more resistant to the usual antiproliferative and proapoptotic effects of histone deacetylase inhibitors. As such drugs may serve as therapeutic agents for cancer, our findings support the use of HDAC2 mutational status in future pharmacogenetic treatment of these individuals.",
    keywords = "311 Basic medicine",
    author = "Santiago Ropero and Fraga, {Mario F} and Esteban Ballestar and Richard Hamelin and Hiroyuki Yamamoto and Manuel Boix-Chornet and Rosalia Caballero and Miguel Alaminos and Fernando Setien and Paz, {Maria F} and Michel Herranz and Jose Palacios and Diego Arango and {\O}rntoft, {Torben F} and Aaltonen, {Lauri A} and Simo Schwartz and Manel Esteller",
    year = "2006",
    doi = "10.1038/ng1773",
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    Ropero, S, Fraga, MF, Ballestar, E, Hamelin, R, Yamamoto, H, Boix-Chornet, M, Caballero, R, Alaminos, M, Setien, F, Paz, MF, Herranz, M, Palacios, J, Arango, D, Ørntoft, TF, Aaltonen, LA, Schwartz, S & Esteller, M 2006, 'A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition', Nature Genetics, vol. 38, no. 5, pp. 566-569. https://doi.org/10.1038/ng1773

    A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. / Ropero, Santiago; Fraga, Mario F; Ballestar, Esteban; Hamelin, Richard; Yamamoto, Hiroyuki; Boix-Chornet, Manuel; Caballero, Rosalia; Alaminos, Miguel; Setien, Fernando; Paz, Maria F; Herranz, Michel; Palacios, Jose; Arango, Diego; Ørntoft, Torben F; Aaltonen, Lauri A; Schwartz, Simo; Esteller, Manel.

    In: Nature Genetics, Vol. 38, No. 5, 2006, p. 566-569.

    Research output: Contribution to journalArticleScientificpeer-review

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    T1 - A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition

    AU - Ropero, Santiago

    AU - Fraga, Mario F

    AU - Ballestar, Esteban

    AU - Hamelin, Richard

    AU - Yamamoto, Hiroyuki

    AU - Boix-Chornet, Manuel

    AU - Caballero, Rosalia

    AU - Alaminos, Miguel

    AU - Setien, Fernando

    AU - Paz, Maria F

    AU - Herranz, Michel

    AU - Palacios, Jose

    AU - Arango, Diego

    AU - Ørntoft, Torben F

    AU - Aaltonen, Lauri A

    AU - Schwartz, Simo

    AU - Esteller, Manel

    PY - 2006

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    N2 - Disruption of histone acetylation patterns is a common feature of cancer cells, but very little is known about its genetic basis. We have identified truncating mutations in one of the primary human histone deacetylases, HDAC2, in sporadic carcinomas with microsatellite instability and in tumors arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. The presence of the HDAC2 frameshift mutation causes a loss of HDAC2 protein expression and enzymatic activity and renders these cells more resistant to the usual antiproliferative and proapoptotic effects of histone deacetylase inhibitors. As such drugs may serve as therapeutic agents for cancer, our findings support the use of HDAC2 mutational status in future pharmacogenetic treatment of these individuals.

    AB - Disruption of histone acetylation patterns is a common feature of cancer cells, but very little is known about its genetic basis. We have identified truncating mutations in one of the primary human histone deacetylases, HDAC2, in sporadic carcinomas with microsatellite instability and in tumors arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. The presence of the HDAC2 frameshift mutation causes a loss of HDAC2 protein expression and enzymatic activity and renders these cells more resistant to the usual antiproliferative and proapoptotic effects of histone deacetylase inhibitors. As such drugs may serve as therapeutic agents for cancer, our findings support the use of HDAC2 mutational status in future pharmacogenetic treatment of these individuals.

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    Ropero S, Fraga MF, Ballestar E, Hamelin R, Yamamoto H, Boix-Chornet M et al. A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Nature Genetics. 2006;38(5):566-569. https://doi.org/10.1038/ng1773