Of the heritable mutations identified in the TP53 gene approximately 7-24% are de novo rather than being inherited.r
Studies indicate that the majority of breast cancer in TP53 carriers are HER2 positive, however the clinical utility of using HER2 status in isolated early onset cases of breast cancer to select for TP53 germline testing is currently unknown.
Increasing evidence suggests that young onset anaplastic rhabdomyosarcoma and sonic hedgehog subtype medulloblastoma are associated with a high rate of heritable TP53 mutations. Some of these data may represent an over-estimation due to ascertainment bias.
||Probability of detecting a heritable mutation
|Classical Li-Fraumeni clinical criteria met (link to TP53 testing criteria)
|Li-Fraumeni like clinical criteria (link to TP53 testing criteria)
|Chompret (2001) or modified Chompret (2009) testing criteria met (link to TP53 testing criteria - see history icon)
|Isolated childhood adrenocortical tumour
||up to 50%r
|Isolated childhood choroid plexus carcinoma
|Isolated breast cancer under the age of 30 years
|Isolated childhood anaplastic rhabdomyosarcoma
||up to 52%r
|Isolated childhood sonic hedgehog subtype medulloblastoma
|Patient has a first or second degree relative with documented pathogenic mutation