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Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy
Rani Bansal1, Tolulope Adeyelu2, Andrew Elliott2
1Duke Cancer Institute, Duke University Hospital, Durham, NC.
JCO Precision Oncology
|December 5, 2024
Summary
Malignant phyllodes tumors (MPTs) harbor actionable molecular alterations, including a TPM4:NTRK1 fusion, suggesting targeted therapies may benefit patients. Comprehensive next-generation sequencing (NGS) is crucial for identifying these opportunities.
Area of Science:
- Oncology
- Genomics
- Molecular Pathology
Background:
- Malignant phyllodes tumors (MPTs) are rare breast cancers with aggressive behavior and high recurrence rates.
- Current treatment relies on surgery, but targeted therapies show promise.
- Understanding the molecular landscape of MPTs is essential for identifying new treatment strategies.
Purpose of the Study:
- To investigate the molecular characteristics of MPTs.
- To identify potential therapeutic targets for MPT management.
- To explore differences in molecular profiles between primary and metastatic sites.
Main Methods:
- Genomic and whole-transcriptome sequencing were performed on 57 MPT samples.
- Immunohistochemistry for PD-L1 and HER2 was conducted.
- Immune cell fractions in the tumor microenvironment were analyzed using quanTIseq.
Main Results:
- MPTs showed low ERBB2 expression, similar to HER2-negative breast cancer.
- Frequent alterations included TERT promoter, MED12, TP53, and NF1 mutations.
- A TPM4:NTRK1 fusion was identified, leading to a clinical response with larotrectinib.
Conclusions:
- The study identified actionable molecular alterations in MPTs, including a TPM4:NTRK1 fusion.
- Comprehensive next-generation sequencing (NGS) with RNA analysis is recommended for MPTs.
- These findings support the development of targeted therapies for MPT patients.
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