The Polycomb complex is integral to epigenetic regulation and is composed of highly conserved proteins; although many redundant Polycomb group proteins exist in mammals, the Polycomb complex gene ph encodes most components in Drosophila. Therefore, Parreno et al. developed a temperature-controlled system to knock down expression of ph in Drosophila larval eye imaginal discs and set out to determine whether transiently disrupting epigenetic regulation could irreversibly lead to cancer.

Consistent with prior work, constitutive knockdown of ph caused tumour formation in all tissues examined. However, the authors found that transient knockdown (multiple timepoints in larval development were surveyed) also caused tumorigenesis, which persisted after recovery of ph expression. To test whether the tumour formation was due to genetic mutations induced by ph knockdown, the team performed whole-genome sequencing and immunofluorescence of markers of genome instability. These experiments found no evidence of genetic driver mutations, which led the authors to deem these tumours epigenetically induced cancers.