DNA methylation profile in pediatric patients with germ cell tumors

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  • Presentation type: Oral
  • Track: Master's
  • Keywords: Childhood cancer; germ cell tumors; DNA methylation; cancer epigenetics;
  • 1 Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
  • 2 Molecular Diagnostic Laboratory, Barretos Cancer Hospital, Barretos, SP, Brazil
  • 3 Children’s Cancer Hospital. Barretos Cancer Hospital. São Paulo, Brazil
  • 4 Barretos Children’s Cancer Hospital, Barretos, São Paulo, Brazil
  • 5 Faculty of Medicine of Ribeirão Preto - USP, Ribeirão Preto, SP, Brazil
  • 6 Molecular Oncology Research Center. Barretos Cancer Hospital. São Paulo, Brazil

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Abstract

Background: Childhood cancer represents the leading cause of disease-related mortality in children, and germ cell tumors (GCTs) account for 3.6% of cases. Although cisplatin is the standard treatment, 15–20% of patients exhibit therapeutic resistance. Moreover, the diagnosis of GCTs relies on tumor markers with low specificity and histopathological analysis by a pathologist with expertise in the field, which limits accurate and timely diagnosis. Consequently, there is scarce knowledge regarding the molecular mechanisms involved in the pathophysiology of these tumors in children, particularly concerning DNA methylation patterns. Aim: To analyze the DNA methylation profile in pediatric patients with GCTs. Methodology: For this purpose, 13 samples from pediatric patients with GCTs treated at the Barretos Children’s Cancer Hospital were selected, subjected to DNA extraction, and their methylation profile were evaluated using the Illumina MethylationEPIC v2.0 Kit. Methylation data, quality metrics and statistical analyses were conducted using RStudio. Results: To date, 13 cryopreserved samples have been hybridized on BeadChips and demonstrated satisfactory quality based on 17 quality metrics and Noob normalization, representing the Beta distribution density. Most patients were female (61.5%) with a median age of 13.8 years. Regarding the primary tumor location, 53.8% were ovarian, followed by 38.5% testicular, and 7.7% sacrococcygeal. Additionally, 46.1% of patients were classified as high-risk, 76.9% had no metastasis at diagnosis, and 84.6% did not present recurrence and received postoperative chemotherapy. Most patients (92.3%) are currently alive. The histologies represented among these 13 samples included 8 mixed germ cell tumors, 2 dysgerminomas, 2 yolk sac tumors, and 1 immature teratoma. Conclusion: The elucidation of the DNA methylation profile in pediatric patients with GCTs will contribute to the literature and provide insights into the epigenetic behavior across different tumor subtypes.

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