A recurrent mutation in PALB2 in Finnish cancer families

Hannele Erkko, Bing Xia, Jenni Nikkilä, Johanna Schleutker, Kirsi Syrjäkoski, Arto Mannermaa, Anne Kallioniemi, Katri Pylkäs, Sanna-Maria Karppinen, Katrin Rapakko, Alexander Miron, Qing Sheng, Guilan Li, Henna Mattila, Daphne W Bell, Daniel A Haber, Mervi Grip, Mervi Reiman, Arja Jukkola-Vuorinen, Aki MustonenJuha Kere, Lauri A Aaltonen, Veli-Matti Kosma, Vesa Kataja, Ylermi Soini, Ronny I Drapkin, David M Livingston, Robert Winqvist

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer(1-3). Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified(4). The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity(4). Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development.
    Original languageEnglish
    JournalNature
    Volume446
    Issue number7133
    Pages (from-to)316-319
    Number of pages4
    ISSN0028-0836
    DOIs
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Erkko, H., Xia, B., Nikkilä, J., Schleutker, J., Syrjäkoski, K., Mannermaa, A., ... Winqvist, R. (2007). A recurrent mutation in PALB2 in Finnish cancer families. Nature, 446(7133), 316-319. https://doi.org/10.1038/nature05609
    Erkko, Hannele ; Xia, Bing ; Nikkilä, Jenni ; Schleutker, Johanna ; Syrjäkoski, Kirsi ; Mannermaa, Arto ; Kallioniemi, Anne ; Pylkäs, Katri ; Karppinen, Sanna-Maria ; Rapakko, Katrin ; Miron, Alexander ; Sheng, Qing ; Li, Guilan ; Mattila, Henna ; Bell, Daphne W ; Haber, Daniel A ; Grip, Mervi ; Reiman, Mervi ; Jukkola-Vuorinen, Arja ; Mustonen, Aki ; Kere, Juha ; Aaltonen, Lauri A ; Kosma, Veli-Matti ; Kataja, Vesa ; Soini, Ylermi ; Drapkin, Ronny I ; Livingston, David M ; Winqvist, Robert. / A recurrent mutation in PALB2 in Finnish cancer families. In: Nature. 2007 ; Vol. 446, No. 7133. pp. 316-319.
    @article{c8c03cb2774049299ae7a98698846ead,
    title = "A recurrent mutation in PALB2 in Finnish cancer families",
    abstract = "BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer(1-3). Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified(4). The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity(4). Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development.",
    keywords = "311 Basic medicine",
    author = "Hannele Erkko and Bing Xia and Jenni Nikkil{\"a} and Johanna Schleutker and Kirsi Syrj{\"a}koski and Arto Mannermaa and Anne Kallioniemi and Katri Pylk{\"a}s and Sanna-Maria Karppinen and Katrin Rapakko and Alexander Miron and Qing Sheng and Guilan Li and Henna Mattila and Bell, {Daphne W} and Haber, {Daniel A} and Mervi Grip and Mervi Reiman and Arja Jukkola-Vuorinen and Aki Mustonen and Juha Kere and Aaltonen, {Lauri A} and Veli-Matti Kosma and Vesa Kataja and Ylermi Soini and Drapkin, {Ronny I} and Livingston, {David M} and Robert Winqvist",
    year = "2007",
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    pages = "316--319",
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    Erkko, H, Xia, B, Nikkilä, J, Schleutker, J, Syrjäkoski, K, Mannermaa, A, Kallioniemi, A, Pylkäs, K, Karppinen, S-M, Rapakko, K, Miron, A, Sheng, Q, Li, G, Mattila, H, Bell, DW, Haber, DA, Grip, M, Reiman, M, Jukkola-Vuorinen, A, Mustonen, A, Kere, J, Aaltonen, LA, Kosma, V-M, Kataja, V, Soini, Y, Drapkin, RI, Livingston, DM & Winqvist, R 2007, 'A recurrent mutation in PALB2 in Finnish cancer families', Nature, vol. 446, no. 7133, pp. 316-319. https://doi.org/10.1038/nature05609

    A recurrent mutation in PALB2 in Finnish cancer families. / Erkko, Hannele; Xia, Bing; Nikkilä, Jenni; Schleutker, Johanna; Syrjäkoski, Kirsi; Mannermaa, Arto; Kallioniemi, Anne; Pylkäs, Katri; Karppinen, Sanna-Maria; Rapakko, Katrin; Miron, Alexander; Sheng, Qing; Li, Guilan; Mattila, Henna; Bell, Daphne W; Haber, Daniel A; Grip, Mervi; Reiman, Mervi; Jukkola-Vuorinen, Arja; Mustonen, Aki; Kere, Juha; Aaltonen, Lauri A; Kosma, Veli-Matti; Kataja, Vesa; Soini, Ylermi; Drapkin, Ronny I; Livingston, David M; Winqvist, Robert.

    In: Nature, Vol. 446, No. 7133, 2007, p. 316-319.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - A recurrent mutation in PALB2 in Finnish cancer families

    AU - Erkko, Hannele

    AU - Xia, Bing

    AU - Nikkilä, Jenni

    AU - Schleutker, Johanna

    AU - Syrjäkoski, Kirsi

    AU - Mannermaa, Arto

    AU - Kallioniemi, Anne

    AU - Pylkäs, Katri

    AU - Karppinen, Sanna-Maria

    AU - Rapakko, Katrin

    AU - Miron, Alexander

    AU - Sheng, Qing

    AU - Li, Guilan

    AU - Mattila, Henna

    AU - Bell, Daphne W

    AU - Haber, Daniel A

    AU - Grip, Mervi

    AU - Reiman, Mervi

    AU - Jukkola-Vuorinen, Arja

    AU - Mustonen, Aki

    AU - Kere, Juha

    AU - Aaltonen, Lauri A

    AU - Kosma, Veli-Matti

    AU - Kataja, Vesa

    AU - Soini, Ylermi

    AU - Drapkin, Ronny I

    AU - Livingston, David M

    AU - Winqvist, Robert

    PY - 2007

    Y1 - 2007

    N2 - BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer(1-3). Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified(4). The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity(4). Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development.

    AB - BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer(1-3). Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified(4). The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity(4). Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development.

    KW - 311 Basic medicine

    U2 - 10.1038/nature05609

    DO - 10.1038/nature05609

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    SN - 0028-0836

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    Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature. 2007;446(7133):316-319. https://doi.org/10.1038/nature05609