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


    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
    Issue number7133
    Pages (from-to)316-319
    Number of pages4
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

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