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Updated: Mar 6, 2026
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma
Yock Ping Chow1, Lu Ping Tan2, San Jiun Chai1
1Cancer Research Malaysia, 47500 Subang Jaya, Selangor, Malaysia.
Abstract:
In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.
Insights
This study identified key genetic mutations in nasopharyngeal carcinoma (NPC) pathways, revealing potential therapeutic targets. Approximately 72% of NPC samples showed mutations in cancer pathways, suggesting biomarkers for targeted therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Nasopharyngeal carcinoma (NPC) is a significant health concern with limited targeted treatment options.
- Identifying actionable somatic mutations is crucial for developing novel therapeutic strategies in NPC.
Purpose of the Study:
- To identify somatically mutated genes in NPC amenable to targeted therapy.
- To explore the potential of these mutations as predictive biomarkers for targeted treatments.
Main Methods:
- Whole exome sequencing of 10 NPC biopsies and matched bloods.
- Targeted gene panel sequencing (HaloPlex) on an additional 88 NPC samples.
- Validation of identified variants using Sanger sequencing.
Main Results:
- Identified 323 mutations in the initial cohort, with enrichment in lipid signaling pathways.
- Detected 160 additional non-synonymous mutations in a prioritized gene set across 88 samples.
- Confirmed 77 true positive variants, with ~72% of NPC samples harboring mutations in key cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair).
Conclusions:
- Genetic mutations in critical cancer pathways are prevalent in NPC.
- These mutations represent potential predictive biomarkers for guiding targeted therapy selection in NPC patients.
