The Brazilian TP53 mutation (R337H) and sarcomas

Abstract

Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.

Fig 1. Age distribution according to mutational status.

Fig 2. Mutational status according to sarcoma subtype.

Fig 3. Clinical stages among wild-type and mutated cases.

Fig 4. Ancestral profile of all patients analyzed.

Left: Patients with the R337H mutation. Right: Patients with the WT phenotype.

Fig 5. Brazilian map depicting the birthplace of patients with the R337H mutation (numbers in the map describe the number of patients with the R337H mutation who came from that specific state).