With the emergence of RTEL1 mutations in Hoyeraal-Hreidarsson syndrome and variant association with predisposition to a range of brain and other cancers (Sarek et al., 2015, Vannier et al., 2014), it will also be important to examine how signatures of Ht-REC correlate with RTEL1 status in these diseases and whether these events and the associated phenotypes of affected individuals/mouse models can be alleviated by MSH2/6 inhibition. This evidence concerns the gene MSH2 and Hoyeraal-Hreidarsson syndrome.