| Title: |
Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy |
| Authors: |
Kline, Cassie N; Joseph, Nancy M; Grenert, James P; van Ziffle, Jessica; Talevich, Eric; Onodera, Courtney; Aboian, Mariam; Cha, Soonmee; Raleigh, David R; Braunstein, Steve; Torkildson, Joseph; Samuel, David; Bloomer, Michelle; Campomanes, Alejandra G de Alba; Banerjee, Anuradha; Butowski, Nicholas; Raffel, Corey; Tihan, Tarik; Bollen, Andrew W; Phillips, Joanna J; Korn, W Michael; Yeh, Iwei; Bastian, Boris C; Gupta, Nalin; Mueller, Sabine; Perry, Arie; Nicolaides, Theodore; Solomon, David A |
| Source: |
Neuro-Oncology, vol 19, iss 5 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2017 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); 3211 Oncology and Carcinogenesis (for-2020); Pediatric Cancer (rcdc); Biotechnology (rcdc); Human Genome (rcdc); Rare Diseases (rcdc); Brain Disorders (rcdc); Precision Medicine (rcdc); Neurosciences (rcdc); Cancer (rcdc); Pediatric Research Initiative (rcdc); Genetics (rcdc); Orphan Drug (rcdc); Brain Cancer (rcdc); Genetic Testing (rcdc); Cancer Genomics (rcdc); Cancer (hrcs-hc); 3 Good Health and Well Being (sdg); Adolescent (mesh); Adult (mesh); Antineoplastic Agents (mesh); Biomarkers; Tumor (mesh); Brain Neoplasms (mesh); Child (mesh); Child; Preschool (mesh); Female (mesh); Germ-Line Mutation (mesh) |
| Subject Geographic: |
699 - 709 |
| Description: |
Background: Molecular profiling is revolutionizing cancer diagnostics and leading to personalized therapeutic approaches. Herein we describe our clinical experience performing targeted sequencing for 31 pediatric neuro-oncology patients. Methods: We sequenced 510 cancer-associated genes from tumor and peripheral blood to identify germline and somatic mutations, structural variants, and copy number changes. Results: Genomic profiling was performed on 31 patients with tumors including 11 high-grade gliomas, 8 medulloblastomas, 6 low-grade gliomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal ganglioneuroma, 1 choroid plexus carcinoma, 1 chordoma, and 1 high-grade neuroepithelial tumor. In 25 cases (81%), results impacted patient management by: (i) clarifying diagnosis, (ii) identifying pathogenic germline mutations, or (iii) detecting potentially targetable alterations. The pathologic diagnosis was amended after genomic profiling for 6 patients (19%), including a high-grade glioma to pilocytic astrocytoma, medulloblastoma to pineoblastoma, ependymoma to high-grade glioma, and medulloblastoma to CNS high-grade neuroepithelial tumor with BCOR alteration. Multiple patients had pathogenic germline mutations, many of which were previously unsuspected. Potentially targetable alterations were identified in 19 patients (61%). Additionally, novel likely pathogenic alterations were identified in 3 cases: an in-frame RAF1 fusion in a BRAF wild-type pleomorphic xanthoastrocytoma, an inactivating ASXL1 mutation in a histone H3 wild-type diffuse pontine glioma, and an in-frame deletion within exon 2 of MAP2K1 in a low-grade astrocytic neoplasm. Conclusions: Our experience demonstrates the significant impact of molecular profiling on diagnosis and treatment of pediatric brain tumors and confirms its feasibility for use at the time of diagnosis or recurrence. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt2z8992j9; https://escholarship.org/uc/item/2z8992j9; https://escholarship.org/content/qt2z8992j9/qt2z8992j9.pdf |
| DOI: |
10.1093/neuonc/now254 |
| Availability: |
https://escholarship.org/uc/item/2z8992j9; https://escholarship.org/content/qt2z8992j9/qt2z8992j9.pdf; https://doi.org/10.1093/neuonc/now254 |
| Rights: |
public |
| Accession Number: |
edsbas.83C56F41 |
| Database: |
BASE |