Table 1.
Clinical Features of LFS‐Associated Cancers in Carriers of the TP53 p.R337H Mutation
| LFS Core Cancers | TP53 p.R337H Carriers |
|---|---|
| ACTs | This is the most prevalent tumor presentation in the pediatric group. Approximately 78% to 97% of pediatric ACTs in the Brazilian population harbor the TP53 p.R337H variant. 13 , 14 ACTs also develop in adults 14 , 20 and can occur as isolated cases, in families with multiple cases, and in families with a wide range of cancers. 13 , 14 , 19 , 21 , 25 , 27 Metachronous ACTs have been reported, 30 but second primary malignancies after an ACT diagnosis are very rare. 20 There is an excessive risk of breast cancer among mothers of pediatric patients with ACTs. 20 Homozygous p.R337H carriers have been described. 14 , 21 |
| Brain tumors | CPC is the second most prevalent tumor type in children (63% of CPCs are p.R337H). 24 , 25 , 27 Multiple independent cases of CPC associated with homozygous p.R337H carriers have been documented. 20 |
| Breast cancer | This is the most common tumor in adults with frequencies of 0.5% to 8.6%. 32 , 33 The age of onset is later in comparison with LFS‐associated breast cancer. 35 It tends to be negative for HER2. 35 Phyllodes carcinoma has been reported. 20 , 40 Secondary primary malignancies, including contralateral cases, have been documented in 50% of cases and are enriched in carriers of the extended haplotype. 20 |
| Sarcomas | These are rarely observed in pediatric cases. 20 , 25 , 37 Leiomyosarcoma is the histologic type predominant in p.R337H carriers. 37 Sarcomas are prevalent in patients older than 50 years. 37 Sarcomas as primary or secondary malignancies are significantly enriched in carriers of the extended haplotype. 20 |
| Others | Thyroid (mostly papillary carcinomas), kidney, skin, and lung cancers are reported among carriers of the p.R337H variant. 41 , 42 , 43 , 44 |
| Overlapping syndromes | TP53 p.R337H has been observed in patients tested for HBOC. 38 , 39 |
Abbreviations: ACT, adrenocortical tumor; CPC, choroid plexus carcinoma; HBOC, hereditary breast and ovarian cancer syndrome; LFS, Li‐Fraumeni syndrome.