Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: International Pediatric Adrenocortical Tumor Registry

Summary: This study aims to collect demographic and medical information including detailed family history of cancer of children and adolescents with adrenocortical tumors in order to learn more about the clinical and epidemiological aspects, treatment modalities, and outcome of patients with this rare disease, worldwide.
  In addition, investigators at St. Jude Children's Research Hospital (SJCRH) plan to perform molecular studies of tumor cells aimed to clarify the role of the TP53 gene and other genetic pathways in these tumors. They aim to obtain relevant biological material from participants with adrenocortical tumor (ACT), their biological parents, and relatives for determination of the TP53 germline status, molecular studies of the TP53 gene, and other molecular pathways.

Detailed description: Adrenocortical tumors (ACT) are rare cancer types that form in the outer layer of the adrenal gland and are very uncommon in children and teenagers. There is variation in pediatric ACT incidence worldwide. In the United States, only about 25 new cases of ACT per million per year, making this a very rare tumor. However, in southern Brazil, the annual incidence of ACT is 15 times that seen in the United States accounting for 3.4-4.2 per million per year.
  Molecular studies have revealed that the majority of children with ACT, particularly those younger than 4 years of age, have constitutional TP53 mutations and/or imprinting defects at chromosome 11p as observed in Beckwith Wiedemann syndrome (BWS) patients. Some mutations, as exemplified by the R337H TP53 germline mutation, in which the function of the mutant protein is relatively preserved, the history of cancer in the carriers and their families is relatively unremarkable. In other cases, the TP53 mutated gene encodes a functionally-impaired protein that predicts for a pervasive history of familial cancer (Li-Fraumeni syndrome). Therefore, these observations have implications for genetic counseling of families with childhood ACT and underscore the importance of genotype-phenotype correlations in familial cancer syndromes.
  The creation of a rare tumor registry provides a mechanism to collect information that cannot be gathered in a single institution. The analysis of the registry data would permit an overview of the clinical, epidemiological, current treatment standards, and survival data of these patients and thus create opportunities for research. It also may facilitate the development of treatment consensus among investigators who register their patients and help to design future studies. Moreover, the combined Children's Oncology Group (COG) and IPACTR studies are expected to provide meaningful insight into the biology of ACT, including clinical phenotype/genotype relationships, treatment outcome and long-term follow-up data in subjects with this rare tumor. Finally, it would provide data on the long-term consequences of exposure to tumor-secreted androgens (found in more than 80% of the pediatric cases) on children's growth and development.

Eligibility: STRATIFICATION ASSIGNMENT:
  -  Stratum A: participant suspected or confirmed diagnosis of adrenocortical tumor (ACT)
  -  Stratum R: relative of participant with ACT and TP53 mutation who has diagnosis of malignancy
  -  Stratum P: biological parent of participant with ACT
  Inclusion Criteria - Stratum A (participant with ACT):
  -  Age ≤ 21 years old at diagnosis
  -  Suspected or confirmed diagnosis of adrenocortical tumor (adenoma, carcinoma or undefined histology).
  -  Signed informed consent
  Inclusion Criteria - Stratum R (relative):
  -  Any age
  -  Diagnosis of malignant tumor
  -  Signed informed consent
  Inclusion Criteria - Stratum P (parent):
  -  Biological parent of Stratum A participant

Relevance to patient case: not relevant