Analysis of PALB2/FANCN-associated breast cancer families

Marc Tischkowitz, Bing Xia, Nelly Sabbaghian, Jorge S. Reis-Filho, Nancy Hamel, Guilan Li, Erik H. Van Beers, Lili Li, Tayma Khalil, Louise A. Quenneville, Atilla Omeroglu, Aletta Poll, Pierre Lepage, Nora Wong, Petra M. Nederlof, Alan Ashworth, Patricia N. Tonin, Steven A. Narod, David M. Livingston, William D. Foulkes

Research output: Contribution to journalArticlepeer-review

180 Scopus citations


No more than ≈30% of hereditary breast cancer has been accounted for by mutations in known genes. Most of these genes, such as BRCA1, BRCA2, TP53, CHEK2, ATM, and FANCJ/BRIP1, function in DNA repair, raising the possibility that germ line mutations in other genes that contribute to this process also predispose to breast cancer. Given its close relationship with BRCA2, PALB2 was sequenced in affected probands from 68 BRCA1/BRCA2-negative breast cancer families of Ashkenazi Jewish, French Canadian, or mixed ethnic descent. The average BRCAPRO score was 0.58. A truncating mutation (229deIT) was identified in one family with a strong history of breast cancer (seven breast cancers in three female mutation carriers). This mutation and its associated breast cancers were characterized with another recently reported but unstudied mutation (2521deIA) that is also associated with a strong family history of breast cancer. There was no loss of heterozygosity in tumors with either mutation. Moreover, comparative genomic hybridization analysis showed major similarities to that of BRCA2 tumors but with some notable differences, especially loss of 18q, a change that was previously unknown in BRCA2 tumors and less common in sporadic breast cancer. This study supports recent observations that PALB2 mutations are present, albeit not frequently, in breast cancer families. The apparently high penetrance noted in this study suggests that at least some PALB2 mutations are associated with a substantially increased risk for the disease.

Original languageEnglish (US)
Pages (from-to)6788-6793
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Apr 17 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


  • DNA repair
  • Fanconi anemia
  • Hereditary predisposition


Dive into the research topics of 'Analysis of PALB2/FANCN-associated breast cancer families'. Together they form a unique fingerprint.

Cite this