Abstract 2273: The spectrum of germline cancer gene mutations in Central American pediatric cancer
Authors: Jesica M. Godinez Paredes, Claudia Garrido, Patricia Calderón, Isabel Rodríguez, Yi Xie, Jia Liu, Wen Luo, Herbert Higson, Kristine Jones, Hong Lou, Lisa Garland, Dulilio Leytón, Lesly Chapman, Edmundo Torres-González, Julie Sawitzke, Matthew Gianferante, Sandra Luna-Fineman, Veronica Girón, Mauricio Castellanos, Federico Antillón-Klussman, Lisa Mirabello, Gerardo Mejia, Michael Dean
Journal: Cancer Research (2025)

Abstract Pediatric cancers are a diverse set of both hematologic and solid malignancies. Approximately 5% of pediatric cancer cases are caused by known genetic conditions, but little is known about genetic susceptibility in Central American children. Most pediatric leukemia and lymphoma cases have high response and cure rates, and many solid malignancies have better outcomes than similar adult cancers. We evaluated the germline genetic variation of pediatric solid tumor cases in Guatemala and Nicaragua in reference hospitals, capturing most of the cancer cases nationwide. We performed exome sequencing on 1360 subjects (957 with solid tumors and 405 with leukemias) and classified variants using an automated pipeline using ClinVar and InterVar and by manual review. The most prevalent cancer types were acute lymphocytic leukemia (357), Hodgkin's lymphoma (229), osteosarcoma (119), and retinoblastoma (93). Pathogenic mutations were identified in 25 pediatric cancer susceptibility genes. Excluding retinoblastoma, 6.5% of cases had a Pathogenic or Likely Pathogenic germline mutation in a cancer-predisposing gene. As expected, RB1 mutations were frequent in retinoblastoma patients, with 81% of confirmed bilateral cases having a Pathogenic or Likely Pathogenic mutation. Mutations in the NF1 gene were observed in neurofibromatosis cases and non-rhabdomyosarcoma. TP53 mutations were observed in osteosarcoma and rhabdomyosarcoma cases, and WT1 mutations were observed in Wilms tumor and renal cancer cases. A single case of pheochromocytoma was found to have a novel VHL gene mutation. Higher rates of pediatric Hodgkin's lymphoma (HL) are found in Central American countries, and the cause of this is unknown. We did not find a significantly mutated gene in the HL cases, suggesting that a common germline mutation is not a significant factor. In conclusion, 6.5% of Central American solid tumor cases have a germline mutation in genes known or suspected to influence cancer risk. Citation Format: Jesica M. Godinez Paredes, Claudia Garrido, Patricia Calderón, Isabel Rodríguez, Yi Xie, Jia Liu, Wen Luo, Herbert Higson, Kristine Jones, Hong Lou, Lisa Garland, Dulilio Leytón, Lesly Chapman, Edmundo Torres-González, Julie Sawitzke, Matthew Gianferante, Sandra Luna-Fineman, Veronica Girón, Mauricio Castellanos, Federico Antillón-Klussman, Lisa Mirabello, Gerardo Mejia, Michael Dean. The spectrum of germline cancer gene mutations in Central American pediatric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2273.