Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology.

Autor:	Beg S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Bareja R; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, United States., Ohara K; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Eng KW; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, United States., Wilkes DC; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Pisapia DJ; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Zoughbi WA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Kudman S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Zhang W; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States., Rao R; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Manohar J; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Kane T; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Sigouros M; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Xiang JZ; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States., Khani F; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Robinson BD; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States., Faltas BM; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States; Department of Medicine, Weill Cornell Medicine, New York, NY, United States., Sternberg CN; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States; Department of Medicine, Weill Cornell Medicine, New York, NY, United States., Sboner A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, United States., Beltran H; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States; Department of Medicine, Weill Cornell Medicine, New York, NY, United States., Elemento O; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, United States., Mosquera JM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United States. Electronic address: jmm9018@med.cornell.edu.
Jazyk:	angličtina
Zdroj:	Translational oncology [Transl Oncol] 2021 Jan; Vol. 14 (1), pp. 100944. Date of Electronic Publication: 2020 Nov 12.
DOI:	10.1016/j.tranon.2020.100944
Abstrakt:	Background: Frequency of clinically relevant mutations in solid tumors by targeted and whole-exome sequencing is ∼30%. Transcriptome analysis complements detection of actionable gene fusions in advanced cancer patients. Goal of this study was to determine the added value of anchored multiplex PCR (AMP)-based next-generation sequencing (NGS) assay to identify further potential drug targets, when coupled with whole-exome sequencing (WES). Methods: Selected series of fifty-six samples from 55 patients enrolled in our precision medicine study were interrogated by WES and AMP-based NGS. RNA-seq was performed in 19 cases. Clinically relevant and actionable alterations detected by three methods were integrated and analyzed. Results: AMP-based NGS detected 48 fusions in 31 samples (55.4%); 31.25% (15/48) were classified as targetable based on published literature. WES revealed 29 samples (51.8%) harbored targetable alterations. TMB-high and MSI-high status were observed in 12.7% and 1.8% of cases. RNA-seq from 19 samples identified 8 targetable fusions (42.1%), also captured by AMP-based NGS. When number of actionable fusions detected by AMP-based NGS were added to WES targetable alterations, 66.1% of samples had potential drug targets. When both WES and RNA-seq were analyzed, 57.8% of samples had targetable alterations. Conclusions: This study highlights importance of an integrative genomic approach for precision oncology, including use of different NGS platforms with complementary features. Integrating RNA data (whole transcriptome or AMP-based NGS) significantly enhances detection of potential targets in cancer patients. In absence of fresh frozen tissue, AMP-based NGS is a robust method to detect actionable fusions using low-input RNA from archival tissue. Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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