Fanconi Anaemia, Childhood Cancer and the BRCA Genes

Genes (Basel). 2021 Sep 27;12(10):1520. doi: 10.3390/genes12101520.


Fanconi 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.

Keywords: BRCA1; BRCA2; childhood cancer; fanconi anaemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Child
  • Child, Preschool
  • Fanconi Anemia / genetics*
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genes, Tumor Suppressor
  • Genetic Predisposition to Disease
  • Humans
  • Mutation
  • Neoplasms / genetics*