Work

Mpth-46. a Pilot Study Identifying Circulating Cell-free Tumor Dna Alterations in Patients With Glioblastoma

Year: 2016

Type: article

Abstract: Liquid biopsy represents a minimally-invasive blood test that is able to detect circulating tumor cells and circulating cell-free DNA (cfDNA), as well as larger fragments of tumor shed in the bloodstream from primary and metastatic solid tumors. It is an important modality to measure residual disease in patients with solid tumors, monitor disease progression and response to treatment. In primary brain tumors, the central nervous system (CNS) poses a challenge to tumor cell/cfDNA shedding due to the presence of the blood brain barrier. The primary goal of this work was to determine if patients with GBM have detectable circulating free tumor DNA (cft) in the bloodstream using deep, next generation sequencing (NGS). Sixteen resected glioblastoma specimens and matched plasma samples were sequenced using the commercially available 50-gene panel library Ion AmpliSeq™Cancer Hotspot Panel v2 (ThermoFisher) on an Ion Proton sequencer. All plasma samples were collected post-surgery of which 2 were collected post-adjuvant treatment. Time from tumor resection to plasma collection ranged from 13 to 284 (median=28.5) days. Thirty three genetic alterations were identified in tissues (16 somatic mutations, 9 polymorphisms, 8 variants). Somatic mutations/variants involved the following genes: TP53 (most common, 11/33, 33%), PTEN, BRAF, IDH1, NRAS, RET, APC, KDR, RB1, ERBB2, PTPN11. Most alterations were single nucleotide variants (n=31, 94%), the rest were indels (n=2, 6.5%). Of these 17 (51.51%) were detected in patient matched plasma samples (9 polymorphisms, 5 variants, 3 somatic mutations). All polymorphisms detected in tissues were detected in plasma. In conclusion, patients with glioblastoma have detectable cftDNA in the blood by NGS. Liquid biopsy in patients with glioblastoma could be used to phenotype tumors in unresectable patients, and to monitor disease progression and response to treatment.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/now212.481