Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy.
作者信息
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
机构信息
Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California San Francisco (UCSF), San Francisco, California, USA.
Department of Pathology, UCSF, San Francisco, California, USA.
出版信息
Neuro Oncol. 2017 May 1;19(5):699-709. doi: 10.1093/neuonc/now254.
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.
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