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Evaluation of ultra-deep targeted sequencing for personalized breast cancer care
Introduction:
The increasing number of targeted therapies, together with a deeper understanding of cancer genetics and drug response, have prompted major healthcare centers to implement personalized treatment approaches relying on high-throughput tumor DNA sequencing. However, the optimal way to implement this transformative methodology is not yet clear. Current assays may miss important clinical information such as the mutation allelic fraction, the presence of sub-clones or chromosomal rearrangements, or the distinction between inherited variants and somatic mutations. Here, we present the evaluation of ultra-deep targeted sequencing (UDT-Seq) to generate and interpret the molecular profile of 38 breast cancer patients from two academic medical centers.
Methods:
We sequenced 47 genes in matched germline and tumor DNA samples from 38 breast cancer patients. The selected genes, or the pathways they belong to, can be targeted by drugs or are important in familial cancer risk or drug metabolism.
Results:
Relying on the added value of sequencing matched tumor and germline DNA and using a dedicated analysis, UDT-Seq has a high sensitivity to identify mutations in tumors with low malignant cell content. Applying UDT-Seq to matched tumor and germline specimens from the 38 patients resulted in a proposal for at least one targeted therapy for 22 patients, the identification of tumor sub-clones in 3 patients, the suggestion of potential adverse drug effects in 3 patients and a recommendation for genetic counseling for 2 patients.
Conclusion:
Overall our study highlights the additional benefits of a sequencing strategy, which includes germline DNA and is optimized for heterogeneous tumor tissues.
Insights
Ultra-deep targeted sequencing (UDT-Seq) of matched tumor and germline DNA improves personalized breast cancer treatment by identifying actionable mutations and tumor heterogeneity. This approach enhances targeted therapy selection and genetic counseling recommendations.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Personalized cancer treatment relies on high-throughput tumor DNA sequencing.
- Current assays may miss crucial clinical information like mutation allelic fraction and tumor sub-clones.
- Ultra-deep targeted sequencing (UDT-Seq) is evaluated for comprehensive molecular profiling.
Purpose of the Study:
- To evaluate the efficacy of UDT-Seq in generating and interpreting molecular profiles of breast cancer patients.
- To assess the added value of sequencing matched tumor and germline DNA for personalized medicine.
Main Methods:
- Sequencing of 47 cancer-related genes in matched germline and tumor DNA from 38 breast cancer patients.
- Utilizing UDT-Seq for high-sensitivity mutation detection, including in tumors with low malignant cell content.
Main Results:
- UDT-Seq identified potential targeted therapies for 22 patients.
- Tumor sub-clones were detected in 3 patients, and potential adverse drug effects were suggested for 3 patients.
- Recommendations for genetic counseling were made for 2 patients.
Conclusions:
- UDT-Seq provides high sensitivity for detecting clinically relevant mutations in heterogeneous tumor tissues.
- A sequencing strategy incorporating germline DNA offers significant benefits for personalized breast cancer treatment.
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