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- Title
A recurrent mutation in PALB2 in Finnish cancer families.
- Authors
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
- Abstract
BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer. Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified. The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity. 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.
- Publication
Nature, 2007, Vol 446, Issue 7133, p316
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature05609