DNA damage repair in Fanconi Anaemia

Dr Stefan Meyer leads the multidisciplinary care for children with Fanconi Anaemia at the Royal Manchester Children’s Hospital and looks after children with other syndrome-associated cancers.

Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities and extreme cancer predisposition. FA results form a defect in one of the at least 16 FA genes that encode for proteins interacting in a fundamental DNA damage response pathway with an important role in development, haematopoiesis and cancer prevention. His research is focused on malignant transformation associated with FA and functional aspects of the FA-pathway in sporadic cancers.

Using FA-derived AML cell lines his group have identified activation of the EVI1 oncogene associated with FA characteristic gains in the chromosomal region 3q26q29. EVI1 function and regulation is complex and includes transforming growth factor (TGF)-β antagonistic and chromatin remodelling properties. Dr Meyer’s group are exploring EVI1 function in the context of the FA defect. The group’s FA-derived AML cell lines, derived from AML associated with bi-allelic disruption of the FANCD1/BRCA2 gene, maintain the FA characteristic cross linker hypersensitivity. They explore the characteristics of the DNA damage response using systems biology approaches in order to identify regulatory events that might be therapeutically accessible.