@article{5fdec98b4e0b45829385c7aad73cb997,
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. 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.",
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 Karppinen, \{Sanna Maria\} 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 Kosma, \{Veli Matti\} and Vesa Kataja and Ylermi Soini and Drapkin, \{Ronny I.\} and Livingston, \{David M.\} and Robert Winqvist",
note = "Funding Information: Acknowledgements We thank J. Ignatius, E. Nieminen, K. Mononen, H. Konola, O. Kajula, M. Vahera, K. Holli, T. Tammela, K. Rouhento, L. Enroth, R. Vaalavuo and S. Marttinen for help in sample and data collection and technical assistance. We also thank the Finnish Red Cross Blood Service for help with collection of population control blood samples, the Finnish Cancer Registry for information on cancer occurrence, and all patients and their family members for volunteering to participate in these studies. This study was supported by the Foundation for the Finnish Cancer Institute, the Academy of Finland, the Ida Montin Foundation, the Cancer Foundation of Northern Finland, the University of Oulu, Oulu University Hospital, the Reino Lahtikari Foundation, the Sigrid Juselius Foundation, Competitive Research Funding of the Pirkanmaa Hospital District, and grants to D.M.L. from the National Cancer Institute. This work was also supported by a grant from the Shapiro Family Foundation. D.M.L. is a scientific consultant to and a grant recipient of The Novartis Institute for Biomedical Research.",
year = "2007",
month = mar,
day = "15",
doi = "10.1038/nature05609",
language = "American English",
volume = "446",
pages = "316--319",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7133",
}