Faculty

Sonir Roberto Rauber Antonini

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Molecular Basis of Adrenocortical Tumours (CAT)

Although pediatric adrenocortical tumors (pACT) are rare (0.2-0.3 individuals younger than 14 years of age per million per year), pediatric endocrinologists frequently face the possibility of a pACT in patients presenting with precocious pubarche, with or without signs of hypercortisolism. Moreover, when investigating a patient with excessive weight gain and growth stunt, the diagnosis of a pACT also is a possibility.

pACT present distinct clinical and histopathological features from the disease in adults. Pediatric patients usually present with functional tumors and signs of excessive hormone secretion, mainly virilization. Most pACT are classified as adrenocortical carcinomas (ACC) based on histopathological findings. The only curative treatment for patients with localized disease is surgical resection. Children with completely resected tumors present a 5-year survival of around 80–90%, while those with residual or metastatic disease have a 5-year survival closer to 0–15%.

pACT display complex genomic background and lack robust prognostic and predictive biomarkers. Mutations in the TP53 gene are frequent in pACT. The germline P53 p.R337H variant is prevalent in Southern Brazil and accounts for the high local incidence of the disease. pACT harboring this mutation and those harboring other TP53 germline mutations display a similar genomic profile in terms of chromosomal gains and losses. Abnormal Wnt/B-catenin pathway activation, with or without betacatenin mutations are also frequent in pACT and result in unfavorable outcomes for these patients. pACT have other molecular hallmarks, like alterations in chromosome 11p15, IGF2 overexpression, mutations in the ATRX gene, and errors in telomere length maintenance. However, isolated, these molecular marks do not have prognostic relevance, but once accumulated, represent a complex interplay in patients with unfavorable outcomes.

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