Novel germline PALB2 truncating mutations in African American breast cancer patients

Cancer. 2012 Mar 1;118(5):1362-70. doi: 10.1002/cncr.26388. Epub 2011 Aug 26.


Background: It has been demonstrated that the partner and localizer of breast cancer 2 (PALB2) acts as a bridging molecule between the breast cancer 1 (BRCA1) and BRCA2 proteins and is responsible for facilitating BRCA2-mediated DNA repair. Truncating mutations in the PALB2 gene reportedly are enriched in patients with Fanconi anemia and breast cancer in various populations.

Methods: The authors evaluated the contribution of PALB2 germline mutations in 279 African American women with breast cancer, including 29 patients with a strong family history, 29 patients with a moderate family history, 75 patients with a weak family history, and 146 patients with nonfamilial or sporadic breast cancer.

Results: After direct sequencing of all the coding exons, exon/intron boundaries, and 5' and 3' untranslated regions of PALB2, 3 novel, monoallelic, truncating mutations (1.08%; 3 in 279 patients) were identified (c.758dupT [exon 4], c.1479delC [exon 4], and c.3048delT [exon 10]) together with 50 sequence variants, 27 of which were novel. None of the truncating mutations were identified in a group of 262 controls from the same population.

Conclusions: PALB2 mutations were present in both familial and nonfamilial breast cancers among African Americans. Rare PALB2 mutations accounted for a small but substantial proportion of patients with breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Americans / genetics*
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma / ethnology
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Codon, Nonsense / genetics
  • DNA Mutational Analysis
  • Family Health
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Gene Frequency
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease / ethnology
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Protein Isoforms / genetics
  • Tumor Suppressor Proteins / genetics*


  • Codon, Nonsense
  • Fanconi Anemia Complementation Group N Protein
  • Nuclear Proteins
  • PALB2 protein, human
  • Protein Isoforms
  • Tumor Suppressor Proteins