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

Fanconi Anaemia, Childhood Cancer and the BRCA Genes

Emma R Woodward  1   2   3 , Stefan Meyer  3   4   5   6
Affiliations
Review

Fanconi Anaemia, Childhood Cancer and the BRCA Genes

Emma R Woodward et al. Genes (Basel). .

Abstract

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Common and diverse clinical and cellular aspects of bi-allelic pathogenic variants in BRCA1 and BRCA2.
See this image and copyright information in PMC

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