Early-onset breast cancer patients in the South and Southeast of Brazil should be tested for the TP53 p.R337H mutation

Abstract

Germline TP53 mutations are associated with Li-Fraumeni syndrome (LFS), a disease that predisposes carriers to a wide variety of early onset tumors. In southern and southeastern Brazil, a high frequency of a germline TP53 mutation, p.R337H, was diagnosed in 0,3% of the population due to a founder effect. Carriers are at risk for developing cancer but the penetrance is lower than in typical DNA binding domain mutations. To date, only a few families were detected and diagnosis of carriers remains a challenge. Therefore, the inclusion of additional criteria to detect p.R337H carriers is necessary for the Brazilian population. We assessed the A.C. Camargo Cancer Center Oncogenetics Department database in search of common characteristics associated with p.R337H families that did not fulfill LFS/LFL clinical criteria. Among 42 p.R337H families, three did not meet any LFS/LFL criteria. All cases were young female patients with breast cancer diagnosed before age 45 and with no family history of LFS linked-cancers. Our results suggest that screening for the germline TP53 p.R337H mutation should be indicated, along with BRCA1 and BRCA2 genetic testing, for this group of patients, especially in the South and Southeast of Brazil.

Figure 1. Pedigrees of the families affected by the germline TP53 p.R337H mutation. A) Family Y0347, B) Family Y0348, C) Family Y0349. The proband is indicated by an arrow; black symbol: patient affected by malignant tumor; yellow symbol: patient carrier of the p.R337H mutation; first information below the symbol: type of tumor and age at diagnosis.