Abstract
Background and aims: The next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited.Methods: Based largely on a protocol approved by the institutional review board at Peking University International Hospital, the current retrospective, single-center study was conducted. Genomic DNA was extracted from blood samples or tumor tissues. With the application of NextSeq 500 instrument (Illumina), Sequencing was performed with an average coverage of 550-fold. Paired-end sequencing was employed utilized with an attempt to achieve improved sensitivity of duplicate detection and therefore to increase the detection reliability of possible fusions.Results: A total of 28 patients (21 men and 7 women) with brain tumors in the present study were involved in the study. The patients enrolled were assigned into two groups, including glioma group (n = 21) and metastatic brain tumor group (n = 7). The mean age of metastatic brain tumor group (59.86 ± 8.85 y), (43.65 ± 13.05 y) reported significantly higher results in comparison to that of glioma group (45.3 ± 12.3 years) (P < 0.05). The mutant genes in metastatic brain tumor group included ALK, MDM2, ATM, BRCA1, FGFR1, MDM4 and KRAS; however, there were no glioma-related mutant genes including MGMT, IDH1, IDH2, 1p/19q, and BRAF et al. Interesteringly, only two patient (28.3%) was detected blood ctDNA in metastatic brain tumor group; In contrast, blood ctDNA was found in ten glioma patients (47.6%) including 1p/19q, MDM2, ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET. The characterizations of IDH mutations in the glioma included IDH1 mutation (p.R132H) and IDH2 mutation (p.R172K). The mutation rate of IDH in tumor tissues was 37.06 ± 8.32%, which was significantly higher than blood samples (P < 0.05).Conclusion: The present study demonstrated that the mutant genes among glioma and metastatic brain tumors are shown to be different. Moreover, the ctDNAs in the metastatic brain tumors included ALK and MDM2, and glioma-related ctDNAs included 1p/19q and MDM2 followed by frequencies of ERBB2, IDH1, CDKN2A, CDK4, PDGFRA, CCNE1, MET. These ctDNAs might be biomarkers and therapeutic responders in brain tumor.
Highlights
Background and aimsThe next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited
In order to be included in the current study, the following inclusion criteria should be met: [1] patients with age ranging from 18 to 75 years old; [2] patients were pathologically confirmed with primary or metastatic brain tumors, and with 5-year cancer-free history; [3] patients with normal functions of multiple vital organs without severe or vital illness; [4] patients scored from 0 to 1 based on the Eastern Cooperative Oncology Group (ECOG); [5] patients were in agreement with complete circulating tumor DNA (ctDNA) tests for tissue or blood samples; [6] informed consent form was signed voluntarily by participants
We found that the mutant genes in the metastatic brain tumors included ALK, MDM2, ATM, BRCA1, FGFR1, and KRAS, and there were no glioma-related mutant genes (MGMT, IDH1, IDH2, 1p/19q, BRAF, and telomerase reverse transcriptase (TERT))
Summary
Background and aimsThe next-generation sequencing technologies and their related assessments of circulating tumor DNA in both glioma and metastatic brain tumors remain largely limited. Metastatic brain tumors are estimated to occur as much as 10 times more frequently in comparison to glioma, which is ∼53.7 per 100,000 persons [4]. Either glioma or metastatic brain tumors are associated with poor prognosis (median overall survival of only 4–15 months), progressive neurological deterioration, and reduced quality of life [5, 6]. The early diagnosis, accurate differentiation, and dynamic monitoring progression of primary and metastatic brain tumors are of great importance. Traditional methods, such as clinical examination, magnetic resonance imaging, and histopathological biopsy, are often limited to meet the requirement for clinical practice [7]
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