Cerebrospinal fluid ctDNA and metabolites are informative biomarkers for the evaluation of CNS germ cell tumors.

Abstract

Serum and cerebrospinal fluid (CSF) levels of α-fetoprotein and β-subunit of human chorionic gonadotropin are used as biomarkers for the management of central nervous system (CNS) germ cell tumors (GCTs). However, additional discriminating biomarkers are required. Especially, biomarkers to differentiate non-germinomatous germ cell tumors (NGGCTs) from germinomas are critical, as these have a distinct prognosis. We investigated CSF samples from 12 patients with CNS-GCT patients (8 germinomas and 4 NGGCTs). We analyzed circulating tumor DNA (ctDNA) in CSF to detect mutated genes. We also used liquid chromatography-mass spectrometry to characterize metabolites in CSF. We detected KIT and/or NRAS mutation, known as frequently mutated genes in GCTs, in 3/12 (25%) patients. We also found significant differences in the abundance of 15 metabolites between control and GCT, with unsupervised hierarchical clustering analysis. Metabolites related to the TCA cycle were increased in GCTs. Urea, ornithine, and short-chain acylcarnitines were decreased in GCTs. Moreover, we also detected several metabolites (e.g., betaine, guanidine acetic acid, and 2-aminoheptanoic acid) that displayed significant differences in abundance in patients with germinomas and NGGCTs. Our results suggest that ctDNA and metabolites in CSF can serve as novel biomarkers for CNS-GCTs and can be useful to differentiate germinomas from NGGCTs.

• Authors: Takeshi Takayasu, Mauli Shah, Antonio Dono, Yuanqing Yan, Roshan Borkar, Nagireddy Putluri, Jay-Jiguang Zhu, Seiji Hama, Fumiyuki Yamasaki, Hidetoshi Tahara, Kazuhiko Sugiyama, Kaoru Kurisu, Yoshua Esquenazi, Leomar Y Ballester
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 14326 (08 31 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32868820 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Circulating Tumor DNA

Topics

• Biomarkers, Tumor (cerebrospinal fluid, genetics)
• Case-Control Studies
• Central Nervous System Neoplasms (cerebrospinal fluid, genetics)
• Circulating Tumor DNA (cerebrospinal fluid, genetics)
• Humans
• Neoplasms, Germ Cell and Embryonal (cerebrospinal fluid, genetics)