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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Beg, S; Bareja, R; Ohara, K; Eng, KW; Wilkes, DC; Pisapia, DJ; Zoughbi, WA; Kudman, S; Zhang, W; Rao, R; Manohar, J; Kane, T; Sigouros, M; Xiang, JZ; Khani, F; Robinson, BD; Faltas, BM; Sternberg, CN; Sboner, A; Beltran, H; Elemento, O; Mosquera, JM.
Integration of whole-exome and anchored PCR-based next generation sequencing significantly increases detection of actionable alterations in precision oncology.
Transl Oncol. 2021; 14(1): 100944
Doi: 10.1016/j.tranon.2020.100944
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- Co-authors Med Uni Graz
- Al-Zoughbi Wael
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- Abstract:
- 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.
- Find related publications in this database (Keywords)
- Anchored multiplex PCR-based
- next-generation sequencing
- Whole-exome sequencing
- RNA Sequencing
- Novel fusion
- Oncogenic