Li-Fraumeni syndrome (LFS) is cancer predisposition disorder with a high risk of having tumors at an early age and multiple primary tumors. LFS is an autosomal dominant disease and germline TP53 mutations were recognized as the main molecular mechanism responsible for the syndrome. LFS is present in 0.3% of the South and Southeastern Brazilian population due to the occurrence of a founder mutation, the p.R337H TP53. This mutation was initially described as tumor specific, predisposing to pediatric adrenocortical carcinoma (ADR). ADR is a rare neoplasm worldwide, but pediatric ADR is 10-15 times more incident in South and Southeast of Brazil, a fact possibly linked to the presence of the p.R337H mutation. To date, the factors that lead to the development of ADR in some children while others remain asymptomatic have not been elucidated and only the presence of the mutation may not be sufficient for tumor appearance.
Therefore, the aim of this study was to evaluate copy number alterations (CNA) of positive ADR patients (N = 3) or negative (N = 1) for p.R337H mutation. Analysis of gains and losses were evaluated by CytoScan HD Array (Affymetrix, Santa Clara, CA, EUA).
In total, 341 alterations were identified (260 gains, 55 losses and 26 LOH), with an average number of 60 alterations in positive cases, while the negative case carried 156 alterations. Among the alterations identified in the positive cases, five of them were recurrent in all samples and involved 5p15.33, 12p13.33, 13q11, 15q11.2 and 19p13.3 regions. Despite the small set of samples, it is evident that positive cases have fewer alterations compared to negative cases.
The apparent higher chromosome instability in negative cases corroborates our previous results in which the presence of p.R337H mutation provides a protective effect in patients with ADR. However, this is a preliminary study and our hypothesis may be confirmed when new investigation in a larger number of samples are completed.
Clinical trial identification
Legal entity responsible for the study
Maria Isabel Achatz
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
All authors have declared no conflicts of interest.