TP53 and cancer: The missense variants clustered in the hot spot central DNA binding domain, which are frequently mutated in cancer (p.R248W: n = 739; p.R273C: n = 707 in somatic IARC TP53 database) and are classified as “contact” mutations, for which the overall architecture of the DNA binding domain is retained, but there is loss of critical DNA contact (Cho et al., 1994; Olivier et al., 2010).