AffiliationManchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester
MetadataShow full item record
AbstractFanconi anaemia (FA) is an inherited chromosomal instability disorder characterised by congenital and developmental abnormalities and a strong cancer predisposition. In less than 5% of cases FA can be caused by bi-allelic pathogenic variants (PGVs) in BRCA2/FANCD1 and in very rare cases by bi-allelic PGVs in BRCA1/FANCS. The rarity of FA-like presentation due to PGVs in BRCA2 and even more due to PGVs in BRCA1 supports a fundamental role of the encoded proteins for normal development and prevention of malignant transformation. While FA caused by BRCA1/2 PGVs is strongly associated with distinct spectra of embryonal childhood cancers and AML with BRCA2-PGVs, and also early epithelial cancers with BRCA1 PGVs, germline variants in the BRCA1/2 genes have also been identified in non-FA childhood malignancies, and thereby implying the possibility of a role of BRCA PGVs also for non-syndromic cancer predisposition in children. We provide a concise review of aspects of the clinical and genetic features of BRCA1/2-associated FA with a focus on associated malignancies, and review novel aspects of the role of germline BRCA2 and BRCA1 PGVs occurring in non-FA childhood cancer and discuss aspects of clinical and biological implications.
CitationWoodward ER, Meyer S. Fanconi Anaemia, Childhood Cancer and the BRCA Genes [Internet]. Vol. 12, Genes. MDPI AG; 2021. p. 1520.
- Fanconi anaemia, BRCA2 mutations and childhood cancer: a developmental perspective from clinical and epidemiological observations with implications for genetic counselling.
- Authors: Meyer S, Tischkowitz M, Chandler K, Gillespie A, Birch JM, Evans DG
- Issue date: 2014 Feb
- Coinheritance of BRCA1 and BRCA2 mutations with Fanconi anemia and Bloom syndrome mutations in Ashkenazi Jewish population: possible role in risk modification for cancer development.
- Authors: Koren-Michowitz M, Friedman E, Gershoni-Baruch R, Brok-Simoni F, Patael Y, Rechavi G, Amariglio N
- Issue date: 2005 Mar
- The Fanconi anaemia/BRCA pathway and cancer susceptibility. Searching for new therapeutic targets.
- Authors: García MJ, Benítez J
- Issue date: 2008 Feb
- Childhood cancer in families with and without BRCA1 or BRCA2 mutations ascertained at a high-risk breast cancer clinic.
- Authors: Brooks GA, Stopfer JE, Erlichman J, Davidson R, Nathanson KL, Domchek SM
- Issue date: 2006 Sep
- Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype.
- Authors: Sawyer SL, Tian L, Kähkönen M, Schwartzentruber J, Kircher M, University of Washington Centre for Mendelian Genomics, FORGE Canada Consortium, Majewski J, Dyment DA, Innes AM, Boycott KM, Moreau LA, Moilanen JS, Greenberg RA
- Issue date: 2015 Feb