Abstract LBA036: Whole-exome sequencing of germ cell tumors in childhood
Authors: Galvão Janaina Mello Soares 
Published: December 2021

Abstract
The germ cell tumors (GCTs) are a rare group of neoplasms that affect about 3.5% of pediatric patients, that comprise both benign and malignant histologies. They are part of a heterogenous group clinically and pathologically complex, derived from totipotent primordial germ cells. Despite their heterogeneity, GCTs can occur in gonadal and extragonadal sites, presenting different histological subtypes. Pediatric cancers in general are known to have low mutational burdens or ‘quiet’ genomes relative to adult tumors, with pediatric malignant tumors having 1,000-fold fewer somatic mutations than several adult cancers. Molecular genetic analyses of pediatric GCT revealed distinct biological differences between childhood GCT compared to those of adults tumors, however, most of those studies have been performed in adult patients, and there is not much knowledge about molecular alterations in children. In contrast to many other solid cancers, previous studies show that GCTs have a relatively low mutational burden which comprise embryonic epigenetic state, copy number alterations (CNAs) and single nucleotide mutation or somatic insertion/deletion (SNV/indel). According to those studies, molecular alterations in the KIT, KRAS and NRAS genes and chromosome 12p amplification are frequently found. Therefore, the aim of this study is to perform a genomic profile by whole-exome sequencing (WES) of pediatric patients diagnosed with GCTs at the Barretos Children’s Cancer Hospital and compare them with adult GCT database. We reported the WES using Illumina paired-end sequencing strategy (&gt;100 X-fold coverage) of sixteen cases and respective matched normal. Data analysis was performed as follows: Mutect, Pindel and Mutsig for SNVs/Indels; HMMcopy, Nexus Copy Number and Gistic for CNAs; and Signal (Cosmic v3) for mutational signatures. The somatic alterations found were compared with data available in the literature and database on adult GCTs. Our samples represent 10 ovarian GCTs, five testicular GCTs and one mediastinal tumor. Somatic mutations in cancer genomes are caused by multiple mutational processes, which may generate a characteristic mutational signature. Analyses of single base substitution signature (SBSS) showed SBSS39 in 11 samples (68,75%) and the SBSS22 in two ovary samples (12,5%). Copy number alterations were observed on chromosomes 4, 7, 8, 10, 12, 21, and 22, with gain of genes KRAS, CCND2, ETV6, KDM5A, MYC, and OLIG2, and loss of genes KIT, FBXW7, PDGFRA, and PTEN. In addition, mutations were observed in following genes MTOR (19%), KIT (12%), CTNNB1 (12%), ATM (12%), KRAS (6%) and PI3KCA (6%). Even though there have been limitations in pediatric CGT studies, our analyzes show that the somatic alterations found correspond to the alterations established in adult CGT and in recent pediatric CGT studies. Therefore, additional whole-exome sequencing studies are necessary to identify and confirm gene mutations associated to pediatric GCT.
Citation Format: Janaina Mello Soares Galvão. Whole-exome sequencing of germ cell tumors in childhood [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA036.