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Updated: May 9, 2026
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
The role of whole-genome sequencing for guiding systemic therapy in patients with soft tissue sarcoma
P van der Laan1, W J van Houdt2, H van Boven3
1Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Background:
The analysis of tumor DNA by whole-genome sequencing (WGS) is increasingly utilized for the identification of clinically relevant DNA aberrations. We aim to assess whether WGS improves the guidance of individualized systemic therapy in soft tissue sarcoma (STS).
Patients And Methods:
WGS results of STS patients were retrieved from electronic patient records and pathology reports from clinical studies and routine diagnostics. WGS was carried out in primary STS with an unfavorable prognosis, metastatic STS, or STS where broad molecular diagnostics were deemed necessary. Actionable targets were defined as genomic alterations identified by WGS for which specific systemic therapy was indicated in routine care or clinical trials available at time of the WGS analysis.
Results:
WGS was carried out on 161 STS patients. The most common histological subtypes were leiomyosarcoma (22%), undifferentiated pleomorphic sarcoma/sarcoma not otherwise specified (17%) and dedifferentiated liposarcoma (14%). The majority of WGS analyses were requested at the time of recurrence or metastasis (41%), At least one actionable target was found by WGS in 74 (46%) of patients. Actionable targets were more frequently seen for complex genome sarcomas compared with simple genome sarcomas (50% versus 28%). Eventually, 23 patients (14%) received matched experimental therapy based on their WGS results. Non-availability of WGS directed treatment or lack of clinical necessity for systemic therapy (n = 17) and rapid disease progression causing poor performance score (n = 10) were the main reasons to not start WGS-informed therapy.
Conclusion:
WGS identified actionable targets in 46% of STS cases, leading to WGS-informed therapy in 14% of patients. Improving the timing of the WGS request and a more appropriate patient selection upfront could increase this relatively low percentage. Complex genome sarcomas seem to be the STS group for which WGS is most likely to add value by opening the way to tumor-agnostic therapies.
Insights
Whole-genome sequencing (WGS) identified actionable targets in 46% of soft tissue sarcoma (STS) cases, guiding therapy in 14%. Optimizing WGS timing and patient selection can enhance its clinical utility, especially for complex genome sarcomas.
Area of Science:
- Oncology
- Genomics
- Medical Diagnostics
Background:
- Whole-genome sequencing (WGS) is increasingly used to detect clinically relevant DNA aberrations in tumors.
- Soft tissue sarcoma (STS) management can benefit from precise molecular diagnostics.
Purpose of the Study:
- To evaluate if whole-genome sequencing (WGS) improves the guidance of individualized systemic therapy for soft tissue sarcoma (STS).
Main Methods:
- WGS data from 161 STS patients were analyzed from electronic records and pathology reports.
- Actionable targets were defined as genomic alterations with available systemic therapy options at the time of WGS.
- WGS was performed on primary STS with poor prognosis, metastatic STS, or when broad molecular diagnostics were necessary.
Main Results:
- Whole-genome sequencing (WGS) identified at least one actionable target in 46% of STS patients.
- Actionable targets were more common in complex genome sarcomas (50%) than simple genome sarcomas (28%).
- Fourteen percent (14%) of patients received WGS-informed therapy, with reasons for not initiating therapy including treatment non-availability or rapid disease progression.
Conclusions:
- Whole-genome sequencing (WGS) is a valuable tool for identifying actionable targets in soft tissue sarcoma (STS), impacting therapy in 14% of cases.
- Improving WGS request timing and patient selection can increase its therapeutic application.
- Complex genome sarcomas represent a promising group for WGS utility, potentially enabling tumor-agnostic therapies.
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