Genomic characterization of intracranial teratomas using whole genome sequencing

Abstract

BackgroundIntracranial teratoma is a rare neoplasm of the central nervous system, often classified into mature and immature types and occurs mainly in children and adolescents. To date, there has been no comprehensive genomic characterization analysis of teratoma due to its rarity of the cases.MethodsForty-six patients with intracranial teratomas were collected and 22 of them underwent whole-exome sequencing, including 8 mature teratomas and 14 immature teratomas. A comprehensive analysis was performed to analyze somatic mutations, copy number variants (CNVs), mutational signatures, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in our cohort.ResultsThe most common somatic mutated gene in intracranial teratomas was CARD11 (18%) and IRS1 (18%), followed by PSMD11, RELN, RRAS2, SMC1A, SYNE1 and ZFHX3, with mutation rates of 14% for the latter six genes. Copy number variation was dominated by amplification, among which ARAF (50%), ATP2B3 (41%), GATA1 (41%), ATP6AP1 (36%), CCND2 (36%) and ZMYM3 (36%) were the most frequently amplified genes. Copy number deletion of SETDB2 and IL2 only appeared in immature teratoma (43% and 36%, respectively), but not in mature teratoma (p = 0.051 and 0.115, respectively). Prognostic analysis showed that TP53 mutations might be associated with poor prognosis of intracranial teratomas patients.ConclusionsOur study revealed the genetic characteristics of intracranial teratoma which might be valuable for guiding future targeted therapies.

Genomic profiling of a metastatic anaplastic melanocytic neuroectodermal tumor arising from a mature thymic teratoma as part of a mediastinal germ cell tumor

“…The first one is p.P222X in the R175–R282 hotspot region of the DNA binding domain of TP53, which is mutated in close to 50% of all human solid cancers ( Chiang et al 2021 ; Marei et al 2021 ). According to a recent genomic study on intracranial teratomas, TP53 is not among the most frequently mutated genes ( Zhang et al 2022 ). Nevertheless, this study showed that the TP53 signaling pathway is affected in 18% of cases and that TP53 mutations might be associated with poor prognosis.…”

“…Nevertheless, this study showed that the TP53 signaling pathway is affected in 18% of cases and that TP53 mutations might be associated with poor prognosis. The role of TP53 alterations on the development of teratoma and malignant somatic transformation is, however, not well-understood ( Zhang et al 2022 ). It has also been shown that TP53 mutations play a crucial role in squamous cell carcinoma arising from ovarian mature cystic teratoma ( Cooke et al 2017 ; Tamura et al 2020 , 2023 ).…”