Genomic landscape of pediatric germ cell tumors reveals oncogenic mutations and copy number alterations

Introduction 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). Methods WES was performed in 16 pediatric GCTs and respective matched normal samples, including ten ovarian, five testicular, and one mediastinal tumor. The somatic alterations found were described and compared with the clinicopathological characteristics, as well as related to molecular databases. Results The somatic mutations found resemble those observed in adult GCTs and recent pediatric GCTs studies. 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. Discussion These findings provide insights into the genomic alterations of pediatric GCTs and emphasize the potential for targeted therapies.