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Friday 23 February 2007

Definition: PALB2 was identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies.

PALB2 co-localizes with BRCA2 (MIM.600185) in nuclear foci, promotes its localization and stability in nuclear structures, and enables its recombinational repair and checkpoint functions. PALB2 is a nuclear binding partner of BRCA2.


Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies.

The phenotype of PALB2 is, in many ways, typical of Fanconi anemia as all cases showed increased chromosome breakage with interstrand crosslinking agents, growth retardation and variable congenital malformations.

- Fanconi anemia

  • Pathogenic truncating PALB2 mutations have been identified in families affected with Fanconi anemia, demonstrating that PALB2 mutations cause a new subtype of Fanconi anemia.

- childhood cancers

  • PALB2 appears to be associated with unusually severe disease and early mortality due to childhood cancer (Wilms tumors, medulloblastomas, AML, neuroblastoma).
  • The cancer spectrum of biallelic PALB2 mutations is very similar to that associated with biallelic BRCA2 mutations, which also confer high risks of embryonal tumors.
  • Mutations in BRCA2 and PALB2 together account for almost all our individuals with both Fanconi anemia and childhood solid tumors.
  • The reasons for the association between childhood solid tumors and the deficiency of BRCA2 or PALB2 are unclear.


Biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer.

- germline mutations in the Fanconi anemia complementation group N results from biallelic mutations in PALB2.

- monoallelic germline PALB2 mutations are associated with:

  • breast cancer susceptibility
    • Germline mutations in PALB2 in African-American breast cancer cases (21113654)

- breast cancer

  • Several population-based and family-based studies have demonstrated that germline mutations of the PALB2 gene (Partner and Localizer of BRCA2) are associated with an increased risk of breast cancer.
  • Truncating PALB2 mutations are found in 0.36% of familial breast cancer cases, a frequency lower than the one detected in comparable studies in other populations (0.73-3.40%). (26564480)
  • it suggests a small but significant contribution of PALB2 mutations to the breast cancer susceptibility in the French population. (26564480)


- Germline mutations in PALB2 in African-American breast cancer cases. Ding YC, Steele L, Chu LH, Kelley K, Davis H, John EM, Tomlinson GE, Neuhausen SL. Breast Cancer Res Treat. 2011 Feb;126(1):227-30. PMID: 21113654

- Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Easton DF, Stratton MR. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007 Feb;39(2):165-7. PMID: 17200668

- Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R, Neveling K, Kelly P, Seal S, Freund M, Wurm M, Batish SD, Lach FP, Yetgin S, Neitzel H, Ariffin H, Tischkowitz M, Mathew CG, Auerbach AD, Rahman N. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007 Feb;39(2):162-4. PMID: 17200671

- Patel KJ. Fanconi anemia and breast cancer susceptibility. Nat Genet. 2007 Feb;39(2):142-3. PMID: 17262024