Gene-20. Multi-gene Mutation Profiling of Pediatric Midline Gliomas Using Patient Liquid Biopsy
Year: 2019
Type: conference-abstract
Abstract: INTRODUCTION: Molecular profiling of the tumor genome is critical for diagnosis and clinical management of CNS tumors. In the case of pediatric diffuse midline gliomas (DMGs), the neuroanatomical location of the tumor precludes surgical resection. Moreover, when tumor resection or biopsy is permitted, serial monitoring of the tumor is limited to MR imaging. We have recently reported on detection of tumor associated somatic mutations in patient liquid biopsy specimens. While powerful, our current approach is limited to multiplexed detection of up to two somatic mutations, limiting comprehensive profiling. To address this, we developed a sensitive approach for profiling tumor genomic aberrations in circulating tumor DNA (ctDNA). RESULTS: We show successful detection of tumor-specific mutations in plasma, serum, and cerebrospinal fluid (CSF) of pediatric DMGs, using a targeted panel to sequence exons of 170 candidate genes. Our analysis indicates overlap of somatic tumor mutations in CSF and plasma with matched tissue; a higher number of mutations were detected in CSF compared to plasma. Patterns of tumor evolution were revealed in CSF analyzed at end-stage disease. For example, loss of a TP53 mutation at progression compared to initial diagnosis was confirmed in CSF collected at postmortem, indicating utility of our platform for identification of tumor evolution. Additionally, subclonal heterogeneity of DMGs was captured in CSF compared to tumor specimens. Low allelic frequency mutations in genes involved in DMG tumorigenesis, such as PI3K signaling and chromatin regulators, were exclusively detected in CSF, but not in matched tumor tissue. IMPACT: Our novel approach enables tumor exome monitoring of low frequency variants in liquid biopsy specimens. Our sensitive targeted sequencing panel provides opportunity for profiling somatic tumor mutations at initial diagnosis and at progression, for mapping tumor evolution in the context of clinical trials.
Source: Neuro-Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2942332824