Cell-free circulating tumor DNA in patients with high-grade glioma as diagnostic biomarker - A guide to future directive

• Published in: Indian journal of cancer Vol. 56; no. 1; pp. 65 - 69
• Main Authors: Ahmed, Khaleel, Govardhan, H, Roy, Manisha, Naveen, T, Siddanna, P, Sridhar, P, Suma, M, Nelson, Noopur
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.01.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd
• Subjects: Adult; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Biopsy; Brain cancer; Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Cancer genetics; Care and treatment; Cell-Free Nucleic Acids - analysis; Cell-Free Nucleic Acids - genetics; Circulating Tumor DNA - analysis; Circulating Tumor DNA - genetics; Deoxyribonucleic acid; Diagnosis; DNA; EDTA; Female; Follow-Up Studies; Genes; Genetic aspects; Genomes; Glioma; Glioma - diagnosis; Glioma - genetics; Gliomas; High-Throughput Nucleotide Sequencing; Humans; Male; Medical imaging; Medical prognosis; Middle Aged; Mutation; Neoplasm Grading; Prospective Studies; Studies; Tumors; Young Adult; India; United States > US; Biomarker; cfTDNA; next-generation sequencing; high-grade glioma
• ISSN: 0019-509X; 1998-4774
• DOI: 10.4103/ijc.IJC_551_17

BACKGROUND: Owing to the aggressive nature of high-grade gliomas (HGGs), its early diagnosis holds the key to a favorable prognosis. Currently, tissue biopsy is the gold standard to verify HGG's initial diagnosis and can be challenging due to its invasive nature. In this study, our objective was a noninvasive panel for timely detection of HGG and its progression using cell-free circulating tumor DNA (cfTDNA). MATERIALS AND METHODS: Twenty-seven patients with HGG were tested with a 50-gene tumor panel. cfTDNA isolated from serum was checked for single-nucleotide variations (SNVs) or copy number alterations using targeted next-generation sequencing, with further validation of results by checking respective formalin-fixed paraffin-embedded tumor tissues for the same genetic alterations. RESULTS: About 88.8% of the patients were detected with HGG-associated cfTDNA. Around 25% patients were detected with one, 25% patients had three, 25% patients had four, and 12.5% patients each had five and six genetic alterations. About 12 of 50 genes were detected in the serum samples. The SNVs detected included TP53 in 87.5% of patients; PIK3CA and EGFR in 50% of patients; PTEN in 37.5%; KIT and VHL in each 25% of patients; and RB1, NF2, MET, ATRX, CDK2A, and CTNNB1 each in 8.3%-16.6%. On combining EGFR, KIT, PTEN, PIK3CA, TP53, and VHL genes (Govardhan Diagnostic Genetic Module for high-grade glioma), at least one of the genetic alterations was found in 100% of patients. Conclusion: These findings illustrate that cfTDNA is easily demonstrable and can be used as a surrogate to tissue biopsy in brain tumor.