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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Pediatric Oncology

Genomic Landscape of Pediatric Germ Cell Tumors Reveals Oncogenic Mutations and Copy Number Alterations

Provisionally accepted
Janaina Mello Soares GalvãoJanaina Mello Soares Galvão1Ana Flavia Souza Peres BezerraAna Flavia Souza Peres Bezerra1Felipe Antonio De Oliveira GarciaFelipe Antonio De Oliveira Garcia1Ana Glenda Santarosa VieiraAna Glenda Santarosa Vieira1Eduardo Caetano Albino Da SilvaEduardo Caetano Albino Da Silva2Andre Van Helvoort LengertAndre Van Helvoort Lengert1Rui Manuel ReisRui Manuel Reis1,3Luiz Fernando LopesLuiz Fernando Lopes4Adriane Feijo EvangelistaAdriane Feijo Evangelista1Mariana Tomazini PintoMariana Tomazini Pinto1*
  • 1Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
  • 2Department of Pathology, Barretos Cancer Hospital, Barretos, Brazil
  • 3Life and Health Sciences Research Institute (ICVS) Medical School, Universidade do Minho, Braga, Portugal
  • 4Children’s Cancer Hospital, Barretos Cancer Hospital, Barretos, Brazil

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Germ cell tumors (GCTs) are rare neoplasms affecting approximately 3.5% of all pediatric patients, with diverse histological subtypes. Despite their clinical and biological heterogeneity, pediatric GCTs generally exhibit a low mutational burden. Compared to adult GCTs, however, the molecular characterization of pediatric cases remains limited, hindering the development of targeted therapeutic strategies. Therefore, we aimed to elucidate the genomic landscape of pediatric GCT patients via whole exome sequencing (WES) followed by bioinformatic analysis, which revealed somatic mutations resembling those found in adult GCTs. Genes with predicted oncogenic variants were found in seven samples (43.75%) out of 16 and included KIT (12.5%), KRAS (6.25%), MTOR (12.5%), PIK3CA (6.25%), AKT2 (6.25%), LARP4B (6.25%), and ACSL6 (6.25%). Copy number alterations were identified on chromosomes 4, 7, 8, 10, 12, 21, and 22, with amplification of CDKN1B, KRAS, CCND2, ETV6, and KDM5A genes, and deletions of KIT and PTEN genes. Clinically significant mutations (KIT: Asp816Val, Ala829Pro; and KRAS: Gln61Leu) suggest potential therapeutic targets for GCT, while MTOR, PIK3CA, and AKT2 emerge as candidates for targeted therapy. These findings provide insights into the genomic alterations of pediatric GCTs and emphasize the potential for targeted therapies.

Keywords: CNA = copy number alteration, Germ cell tumor, Mutation, pediatric tumor, Whole-exome sequencing

Received: 19 Aug 2025; Accepted: 07 Jan 2026.

Copyright: © 2026 Mello Soares Galvão, Souza Peres Bezerra, Garcia, Santarosa Vieira, Da Silva, Van Helvoort Lengert, Reis, Lopes, Evangelista and Tomazini Pinto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mariana Tomazini Pinto

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material