Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia.

The breast cancer susceptibility gene BRCA2 has recently been identified as identical to the Fanconi anemia (FA) gene FANCD1. Here we expand the clinical implications of this discovery. Notably, we identified 6 children in 5 kindreds exhibiting the co-occurrence of BRCA2 mutations, FA, and early onset acute leukemia. Leukemia occurred at a median of 2.2 years of age in the BRCA2 patients in contrast to a median onset of 13.4 years in all other FA patients in the International Fanconi Anemia Registry (IFAR; P <.0001). Breast cancer was noted in 4 of the 5 kindreds. Of the 6 children with leukemia, 4 were treated with bone marrow transplantation and 2 are alive at 3 and 9 months after treatment. Our results suggest that BRCA2 testing should be considered in all patients with FA in whom the complementation group cannot be defined or in whom leukemia is diagnosed at or before 5 years of age.