Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology
| Autor: | Michael Sigouros, Andrea Sboner, Olivier Elemento, Kenneth Wha Eng, Jyothi Manohar, Francesca Khani, Wael Al Zoughbi, Wei Zhang, Sarah Kudman, Jenny Xiang, Bishoy Faltas, Shaham Beg, David Wilkes, David J. Pisapia, Rema Rao, Cora N. Sternberg, Troy Kane, Himisha Beltran, Kentaro Ohara, Brian D. Robinson, Rohan Bareja, Juan Miguel Mosquera |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Original article Cancer Research Computational biology Biology lcsh:RC254-282 DNA sequencing Transcriptome 03 medical and health sciences 0302 clinical medicine Anchored multiplex PCR-based next-generation sequencing Multiplex polymerase chain reaction Oncogenic medicine Exome Exome sequencing RNA Sequencing Novel fusion Cancer Precision medicine medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology Oncology Precision oncology 030220 oncology & carcinogenesis Whole-exome sequencing |
| Zdroj: | Translational Oncology, Vol 14, Iss 1, Pp 100944-(2021) Translational Oncology |
| ISSN: | 1936-5233 |
| Popis: | Highlights • NGS-based clinical studies have reported detection of clinically relevant alterations in ∼30% of patients. • To increase the detection of potential targets, we integrated whole-exome sequencing with a multiplex PCR-based NGS assay for fusion detection. • The targeted transcriptome sequencing was performed using a very low RNA input from archival cancer tissues. • With this integrated approach, we demonstrate a significant increase in detection of targetable genomic alterations in cancer patients. 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. |
| Databáze: | OpenAIRE |
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