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Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kline, Cassie Joseph, Nancy M. Grenert, James P. Ziffle, Jessica Van Talevich, Eric Onodera, Courtney S. Aboian, Mariam Cha, Soonmee Raleigh, David R. Braunstein, Steve Torkildson, Joseph C. Samuel, David Bloomer, Michelle Campomanes, Alejandra G. De Alba Banerjee, Anuradha Butowski, Nicholas A. Raffel, Corey Tihan, Tarik Bollen, A. W. Phillips, Joanna J. Korn, W. Michael Yeh, Iwei Bastian, Boris C. Gupta, Nalin Lochan Mueller, Sabine Perry, Arie Nicolaides, Theodore P. Solomon, David A. |
| Copyright Year | 2017 |
| Abstract | 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1093/neuonc/now254 |
| PubMed reference number | 28453743 |
| Journal | Medline |
| Volume Number | 19 |
| Alternate Webpage(s) | https://escholarship.org/content/qt7gm200jk/qt7gm200jk.pdf?t=plqank |
| Alternate Webpage(s) | https://doi.org/10.1093/neuonc%2Fnow254 |
| Journal | Neuro-oncology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
