Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology
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 (A...
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Format: | Article |
Language: | English |
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Elsevier
2021-01-01
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Series: | Translational Oncology |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523320304368 |
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doaj-8726c544cc9845559727803f01fd27f6 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shaham Beg Rohan Bareja Kentaro Ohara Kenneth Wha Eng David C. Wilkes David J. Pisapia Wael Al Zoughbi Sarah Kudman Wei Zhang Rema Rao Jyothi Manohar Troy Kane Michael Sigouros Jenny Zhaoying Xiang Francesca Khani Brian D. Robinson Bishoy M. Faltas Cora N. Sternberg Andrea Sboner Himisha Beltran Olivier Elemento Juan Miguel Mosquera |
spellingShingle |
Shaham Beg Rohan Bareja Kentaro Ohara Kenneth Wha Eng David C. Wilkes David J. Pisapia Wael Al Zoughbi Sarah Kudman Wei Zhang Rema Rao Jyothi Manohar Troy Kane Michael Sigouros Jenny Zhaoying Xiang Francesca Khani Brian D. Robinson Bishoy M. Faltas Cora N. Sternberg Andrea Sboner Himisha Beltran Olivier Elemento Juan Miguel Mosquera Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology Translational Oncology Anchored multiplex PCR-based next-generation sequencing Whole-exome sequencing RNA Sequencing Novel fusion Oncogenic |
author_facet |
Shaham Beg Rohan Bareja Kentaro Ohara Kenneth Wha Eng David C. Wilkes David J. Pisapia Wael Al Zoughbi Sarah Kudman Wei Zhang Rema Rao Jyothi Manohar Troy Kane Michael Sigouros Jenny Zhaoying Xiang Francesca Khani Brian D. Robinson Bishoy M. Faltas Cora N. Sternberg Andrea Sboner Himisha Beltran Olivier Elemento Juan Miguel Mosquera |
author_sort |
Shaham Beg |
title |
Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology |
title_short |
Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology |
title_full |
Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology |
title_fullStr |
Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology |
title_full_unstemmed |
Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology |
title_sort |
integration of whole-exome and anchored pcr-based next generation sequencing significantly increases detection of actionable alterations in precision oncology |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 |
publishDate |
2021-01-01 |
description |
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. |
topic |
Anchored multiplex PCR-based next-generation sequencing Whole-exome sequencing RNA Sequencing Novel fusion Oncogenic |
url |
http://www.sciencedirect.com/science/article/pii/S1936523320304368 |
work_keys_str_mv |
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doaj-8726c544cc9845559727803f01fd27f62020-12-25T05:07:43ZengElsevierTranslational Oncology1936-52332021-01-01141100944Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncologyShaham Beg0Rohan Bareja1Kentaro Ohara2Kenneth Wha Eng3David C. Wilkes4David J. Pisapia5Wael Al Zoughbi6Sarah Kudman7Wei Zhang8Rema Rao9Jyothi Manohar10Troy Kane11Michael Sigouros12Jenny Zhaoying Xiang13Francesca Khani14Brian D. Robinson15Bishoy M. Faltas16Cora N. Sternberg17Andrea Sboner18Himisha Beltran19Olivier Elemento20Juan Miguel Mosquera21Department 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 StatesCaryl 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 StatesDepartment 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 StatesCaryl 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 StatesDepartment 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 StatesDepartment 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 StatesDepartment 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 StatesDepartment 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 StatesDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United StatesDepartment 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 StatesCaryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United StatesCaryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United StatesCaryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine and NewYork Presbyterian, New York, NY, United StatesDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United StatesDepartment 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 StatesDepartment 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 StatesCaryl 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 StatesCaryl 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 StatesDepartment 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 StatesCaryl 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 StatesCaryl 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 StatesDepartment 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; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1936523320304368Anchored multiplex PCR-based next-generation sequencingWhole-exome sequencingRNA SequencingNovel fusionOncogenic |