Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour

• Published in: Journal of medical genetics Vol. 42; no. 2; pp. 147 - 151
• Main Authors: Reid, S, Renwick, A, Seal, S, Baskcomb, L, Barfoot, R, Jayatilake, H, Pritchard-Jones, K, Stratton, M R, Ridolfi-Lüthy, A, Rahman, N
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.02.2005; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Alleles; Biological and medical sciences; Brain cancer; Brain Neoplasms - genetics; BRCA2; Breast Neoplasms - genetics; Cardiology. Vascular system; Child; familial Wilms tumour; Family medical history; Fanconi anaemia; Fanconi Anemia - genetics; Female; General aspects. Genetic counseling; Genes, BRCA2; Genetic Predisposition to Disease; Health risk assessment; Humans; Kidney Neoplasms - genetics; Kidneys; Letter to JMG; Male; Medical genetics; Medical sciences; medulloblastoma; Mutation; Nephrology. Urinary tract diseases; Pedigree; Siblings; Tumors of the urinary system; Wilms Tumor - genetics; Wilms tumour; Human; Kidney disease; Urinary system disease; Multiple; Family study; Malignancy; Malignant tumor; Association; Wilms tumor; Genetics; Mutation; Child; Tumor suppressor gene
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2004.022673

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. 5 FA 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. In part this may be because affected children present before their parents, as exemplified by WILMS2, in which the mother and paternal aunt developed breast cancer after the boys had died. [...]although a family history may be helpful in the identification of some biallelic BRCA2 families, it will likely need to extend to at least three generations to detect the cancer history, particularly on the paternal side.