Fanconi Anaemia, Childhood Cancer and the Genes.

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 and in very rare cases by bi-allelic PGVs in . The rarity of FA-like presentation due to PGVs in and even more due to PGVs in supports a fundamental role of the encoded proteins for normal development and prevention of malignant transformation. While FA caused by PGVs is strongly associated with distinct spectra of embryonal childhood cancers and AML with -PGVs, and also early epithelial cancers with PGVs, germline variants in the genes have also been identified in non-FA childhood malignancies, and thereby implying the possibility of a role of PGVs also for non-syndromic cancer predisposition in children. We provide a concise review of aspects of the clinical and genetic features of /-associated FA with a focus on associated malignancies, and review novel aspects of the role of germline and PGVs occurring in non-FA childhood cancer and discuss aspects of clinical and biological implications.