PMID- 28663030 OWN - NLM STAT- MEDLINE DCOM- 20170825 LR - 20181202 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 103 IP - 1 DP - 2017 Aug TI - Early experience with formalin-fixed paraffin-embedded (FFPE) based commercial clinical genomic profiling of gliomas-robust and informative with caveats. PG - 87-93 LID - S0014-4800(17)30195-8 [pii] LID - 10.1016/j.yexmp.2017.06.006 [doi] AB - BACKGROUND: Commercial targeted genomic profiling with next generation sequencing using formalin-fixed paraffin embedded (FFPE) tissue has recently entered into clinical use for diagnosis and for the guiding of therapy. However, there is limited independent data regarding the accuracy or robustness of commercial genomic profiling in gliomas. METHODS: As part of patient care, FFPE samples of gliomas from 71 patients were submitted for targeted genomic profiling to one commonly used commercial vendor, Foundation Medicine. Genomic alterations were determined for the following grades or groups of gliomas; Grade I/II, Grade III, primary glioblastomas (GBMs), recurrent primary GBMs, and secondary GBMs. In addition, FFPE samples from the same patients were independently assessed with conventional methods such as immunohistochemistry (IHC), Quantitative real-time PCR (qRT-PCR), or Fluorescence in situ hybridization (FISH) for three genetic alterations: IDH1 mutations, EGFR amplification, and EGFRvIII expression. RESULTS: A total of 100 altered genes were detected by the aforementioned targeted genomic profiling assay. The number of different genomic alterations was significantly different between the five groups of gliomas and consistent with the literature. CDKN2A/B, TP53, and TERT were the most common genomic alterations seen in primary GBMs, whereas IDH1, TP53, and PIK3CA were the most common in secondary GBMs. Targeted genomic profiling demonstrated 92.3%-100% concordance with conventional methods. The targeted genomic profiling report provided an average of 5.5 drugs, and listed an average of 8.4 clinical trials for the 71 glioma patients studied but only a third of the trials were appropriate for glioma patients. CONCLUSIONS: In this limited comparison study, this commercial next generation sequencing based-targeted genomic profiling showed a high concordance rate with conventional methods for the 3 genetic alterations and identified mutations expected for the type of glioma. While it may not be feasible to exhaustively independently validate a commercial genomic profiling assay, examination of a few markers provides some reassurance of its robustness. While potential targeted drugs are recommended based on genetic alterations, to date most targeted therapies have failed in glioblasomas so the usefulness of such recommendations will increase with development of novel and efficacious drugs. CI - Copyright (c) 2017. Published by Elsevier Inc. FAU - Movassaghi, Masoud AU - Movassaghi M AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Shabihkhani, Maryam AU - Shabihkhani M AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Hojat, Seyed A AU - Hojat SA AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Williams, Ryan R AU - Williams RR AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Chung, Lawrance K AU - Chung LK AD - Department of Neurosurgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Im, Kyuseok AU - Im K AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Lucey, Gregory M AU - Lucey GM AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Wei, Bowen AU - Wei B AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Mareninov, Sergey AU - Mareninov S AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Wang, Michael W AU - Wang MW AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Ng, Denise W AU - Ng DW AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Tashjian, Randy S AU - Tashjian RS AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Magaki, Shino AU - Magaki S AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Perez-Rosendahl, Mari AU - Perez-Rosendahl M AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Yang, Isaac AU - Yang I AD - Department of Neurosurgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Khanlou, Negar AU - Khanlou N AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Vinters, Harry V AU - Vinters HV AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Department of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Brain Research Institute, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Liau, Linda M AU - Liau LM AD - Department of Neurosurgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Brain Research Institute, University of California-Los Angeles, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Nghiemphu, Phioanh L AU - Nghiemphu PL AD - Department of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Lai, Albert AU - Lai A AD - Department of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Brain Research Institute, University of California-Los Angeles, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Cloughesy, Timothy F AU - Cloughesy TF AD - Department of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA, United States. FAU - Yong, William H AU - Yong WH AD - Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States; Brain Research Institute, University of California-Los Angeles, Los Angeles, CA, United States; Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA, United States. Electronic address: wyong@mednet.ucla.edu. LA - eng PT - Journal Article DEP - 20170627 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (epidermal growth factor receptor VIII) RN - 1HG84L3525 (Formaldehyde) RN - 8002-74-2 (Paraffin) RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 1.1.1.42. (IDH1 protein, human) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (PIK3CA protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Brain Neoplasms/diagnosis/genetics MH - Class I Phosphatidylinositol 3-Kinases MH - ErbB Receptors/genetics/metabolism MH - Female MH - Formaldehyde/*chemistry MH - *Gene Expression Profiling MH - *Genomics MH - Glioma/*diagnosis/genetics MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Isocitrate Dehydrogenase/genetics/metabolism MH - Male MH - Middle Aged MH - Mutation MH - Paraffin/*chemistry MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Real-Time Polymerase Chain Reaction MH - Tumor Suppressor Protein p53/genetics/metabolism MH - Young Adult OTO - NOTNLM OT - Exome profiling OT - Foundation medicine OT - GBM OT - Genomic profiling OT - Glioma EDAT- 2017/07/01 06:00 MHDA- 2017/08/26 06:00 CRDT- 2017/07/01 06:00 PHST- 2017/04/06 00:00 [received] PHST- 2017/06/24 00:00 [revised] PHST- 2017/06/24 00:00 [accepted] PHST- 2017/07/01 06:00 [pubmed] PHST- 2017/08/26 06:00 [medline] PHST- 2017/07/01 06:00 [entrez] AID - S0014-4800(17)30195-8 [pii] AID - 10.1016/j.yexmp.2017.06.006 [doi] PST - ppublish SO - Exp Mol Pathol. 2017 Aug;103(1):87-93. doi: 10.1016/j.yexmp.2017.06.006. Epub 2017 Jun 27.