Metachronous Medulloblastoma in a Child With Successfully Treated Neuroblastoma: Case Report and Novel Findings of DNA Sequencing

Abstract

Metachronous neoplasms have rarely been reported in patients with neuroblastoma. This report presents the clinical case of a 23-month-old child who was diagnosed with an anaplastic medulloblastoma 5 months after completing treatment for stage IV neuroblastoma. The patient was treated with complete surgical resection and adjuvant chemoradiation followed by maintenance chemotherapy at an outside institution and came to our institution for further management. A pathologic diagnosis and review of both the suprarenal and posterior fossa masses were performed, as well as a genetic analysis of both cerebellar tumor tissue and blood using next-generation gene sequencing. At our institution, the patient was submitted to induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation and remains free of disease 2 years after completion of treatment. Genetic analysis revealed multiple somatic copy number variations with most deleted genes located in 2q37, a region which harbors genes involved in epigenetic regulation and tumor suppression. A homozygous deletion was found in the gene, which is a clinically actionable gene, and patients with activating deletions in can potentially be eligible for basket clinical trials with mTOR inhibitors. Germline single nucleotide variants were also identified in multiple genes involved in cancer , and), cancer predisposition (, and , and genes involved in DNA repair (, and ). Metachronous neoplasms are rare and challenging to treat, hence genetic analysis and referral are needed to exclude hereditary cause. DNA sequencing of the tumor and germline can help identify alterations that increase predisposition or can be used to guide treatment decisions on recurrence and when standard options fail.

Epigenome-wide association study reveals CpG sites related to COG of neuroblastoma

“…Naba et al reported SNED1 as characteristic protein of highly metastatic in mammary carcinoma, and the overexpression of SNED1 was associated with poor outcome for patients with ER−/PR− breast cancer [23]. The homozygous deletions of SNED1 might be involved in tumor metastasis of NB [24], while DNA methylation change of SNED1 was associated with the clinical course of NB [25]. However, the mechanisms of SNED1 involved in invasive phenotype remains unclear.…”