RESUMO
Pediatric high-grade glioma is a rare tumor characterized by high mortality. The authors report the first case of a high-grade glioma associated with a GOPC(FIG)-ROS1 fusion in a pediatric patient. The patient underwent gross-total resection at the age of 4 years, followed by adjuvant high-dose chemotherapy and autologous hematopoietic stem cell rescue. At 30 months after transplantation, she remains disease free.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Proteínas de Transporte/genética , Glioma/genética , Glioma/cirurgia , Proteínas de Membrana/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Pré-Escolar , Feminino , Glioma/diagnóstico por imagem , Glioma/patologia , Proteínas da Matriz do Complexo de Golgi , Humanos , Proteínas de Membrana Transportadoras , Gradação de Tumores , Deleção de Sequência , SobreviventesRESUMO
PURPOSE: A clinical testing cohort was used to gain a broader understanding of the spectrum of tumors associated with germline p53 mutations to aid clinicians in identifying high-risk families. PATIENTS AND METHODS: Full sequencing of the coding exons (2 to 11) and associated splice junctions of the p53 gene was performed on 525 consecutive patients whose blood samples were submitted for diagnostic testing. Clinical features of p53 germline carriers in this cohort were characterized, clinical referral schemes based on reported p53-associated family phenotypes were evaluated, and practical mutation prevalence tables were generated. RESULTS: Mutations were identified in 91 (17%) of 525 patients submitted for testing. All families with a p53 mutation had at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC). Every individual with a choroid plexus tumor (eight of eight) and 14 of 21 individuals with a childhood ACC had a mutation regardless of family history. Based on reported personal and family history, 95% of patients (71 of 75) with a mutation met either classic Li Fraumeni syndrome (LFS) or Chompret criteria. A simplified prevalence table provides a concise summary of individual and family characteristics associated with p53 mutations. CONCLUSION: This is, to our knowledge, the largest single report of diagnostic testing for germline p53 mutations, yielding practical mutation prevalence tables and suggesting clinical utility of classic LFS and Chompret criteria for identifying a subset of cancer-prone families with p53 germline mutations, with important implications for diagnosis and management.
