Fanconi anemia is associated with a defect in the BRCA2 partner PALB2

Abstract

The Fanconi anemia and BRCA networks are considered interconnected, as BRCA2 gene defects have been discovered in individuals with Fanconi anemia subtype D1. Here we show that a defect in the BRCA2-interacting protein PALB2 is associated with Fanconi anemia in an individual with a new subtype. PALB2-deficient cells showed hypersensitivity to cross-linking agents and lacked chromatin-bound BRCA2; these defects were corrected upon ectopic expression of PALB2 or by spontaneous reversion.

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Figure 1: Phenotype of PALB2-deficient cells from an individual with Fanconi anemia is corrected by ectopic expression of PALB2.
Figure 2: PALB2 protein analysis in EUFA1341 and EUFA1341(R) lymphoblasts.

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Acknowledgements

We thank the family of individual EUFA1341 for contributing to this study, M. Makiya and C. de Leon Lucero for help in the collection of clinical data and J. Steltenpool and A. Oostra for expert technical assistance. The members of the Livingston laboratory are grateful to A. D'Andrea and his colleagues at the Dana Farber Cancer Institute for a number of useful discussions and for Fanconi anemia-related reagents. This study was financially supported by the Netherlands Organization for Health Research and Development (J.P.d.W. and N.A.); by grants, including a breast cancer SPORE, from the National Cancer Institute (D.M.L.); by the Breast Cancer Program of US Army Medical Research and Materiel Command (B.X.); by the Intramural Research Program of the National Institute on Aging, US National Institutes of Health (W.W.) and by the Fanconi Anemia Research Fund (H.J.)

Author information

Correspondence to David M Livingston or Johan P de Winter.

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Competing interests

D.M.L is a scientific consultant to and recipient of a research grant from Novartis AG. A.E. is an employee of MRC-Holland BV.

Supplementary information

Supplementary Fig. 1

Deletion screening by MPLA. (PDF 98 kb)

Supplementary Fig. 2

Pedigree of EUFA1341 and cancer cases in the family. (PDF 77 kb)

Supplementary Table 1

Primer information. (PDF 104 kb)

Supplementary Methods (PDF 137 kb)

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Xia, B., Dorsman, J., Ameziane, N. et al. Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet 39, 159–161 (2007). https://doi.org/10.1038/ng1942

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