Biallelic <i>BRCA2</i> mutations are associated with multiple malignancies in childhood including familial Wilms tumour

Abstract

ilms tumour (WT) is an embryonal tumour of the kidney that occurs in 1 in 10 000 children. Familial clusters are rare and account for only 1-3% of cases. ] anconi anaemia (FA, MIM 227650) is a rare autosomal recessive condition affecting ,1 in 300 000 children. FA is characterised by variable congenital abnormalities, short stature, bone marrow failure, hypersensitivity to DNA crosslinking agents, and a predisposition to haematological malignancies such as acute myeloid leukaemia in childhood. A is heterogeneous and consists of at least 11 complementation groups, A, B, C, D1, D2, E, F, G, I, J, and L. 6-8 Eight FA genes have been cloned and at least six FA proteins, FANCA, FANCC, FANCE, FANCF, FANCG, and FANCL, form a nuclear complex required for monoubiquitination of FANCD2. This modification promotes translocation of FANCD2 to DNA repair foci that also contain BRCA1, BRCA2, and RAD51. 9 In 2002, Howlett and colleagues reported biallelic BRCA2 mutations in individuals with Fanconi anaemia D1 (FA-D1). Subsequently, additional FA-D1 and unclassified FA cases were examined and cases with BRCA2 mutations and WT and/or brain tumours were reported.