Early experience with formalin-fixed paraffin-embedded (FFPE) based commercial clinical genomic profiling of gliomas-robust and informative with caveats.

Autor:	Movassaghi M; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Shabihkhani M; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Hojat SA; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Williams RR; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Chung LK; Department of Neurosurgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Im K; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Lucey GM; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Wei B; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Mareninov S; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Wang MW; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Ng DW; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Tashjian RS; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Magaki S; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Perez-Rosendahl M; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Yang I; 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., Khanlou N; Divison of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, United States., Vinters HV; 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., Liau LM; 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., Nghiemphu PL; 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., Lai A; 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., Cloughesy TF; 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., Yong WH; 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.
Jazyk:	angličtina
Zdroj:	Experimental and molecular pathology [Exp Mol Pathol] 2017 Aug; Vol. 103 (1), pp. 87-93. Date of Electronic Publication: 2017 Jun 27.
DOI:	10.1016/j.yexmp.2017.06.006
Abstrakt:	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. (Copyright © 2017. Published by Elsevier Inc.)
Databáze:	MEDLINE
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